bluuebunny/crossref_metadata_2025 huggingface dataset:
Periosteal stripping and periosteal division for leg length discrepancy after proximal femoral intertrochanteric osteotomy for Perthes disease
Authors: Kitta Ayana , Saisu Takashi , Kakizaki Jun , Oikawa Yasuhiro , Segawa Yuko , Okazaki Ken
Published: January 2023

Background: Periosteal stripping and periosteal division (PSPD) promotes growth of the long bone of children with leg length discrepancy (LLD). We performed PSPD when LLD was observed at the time of implant removal surgery after proximal femoral osteotomy for Perthes disease. This study aimed to clarify the efficacy and safety of PSPD for acquired LLD related to Perthes disease.
Methods: This retrospective study enrolled 10 patients treated with PSPD and 6 control patients who declined the PSPD for LLD associated with Perthes disease. The lengths of the femur, tibia and entire leg were measured in the full-length standing radiographs at baseline and final follow-up. Baseline was defined as the time of the last preoperative observation. LLD and changes in LLD (ΔLLD) were measured. The correlation of ΔLLD with age at time of surgery, follow-up period, and extent of PSPD was investigated.
Results: Patients’ mean age and LLD at baseline were 9.4 years and 20.5 ± 4.6 mm in the PSPD group and 10.2 years and 11.5 ± 10.0 mm in the control group. With a mean follow-up period of 4.3 years, the PSPD group showed a mean ΔLLD decrease of 13.9 mm, which was significantly greater than that of the control group at 3.2 mm with a mean follow-up period of 5.4 years. Logistic regression analysis revealed that age at the time of surgery was a significant factor for obtaining >10 mm ΔLLD with PSPD and the cutoff value by the receiver operating characteristic curve was 9.6 years (sensitivity, 0.83; specificity 0.83).
Conclusion: PSPD seemed to be a safe and effective surgical option for LLD associated with Perthes disease. The age at the time of surgery negatively correlated with the amount of LLD correction. Obtaining >10 mm LLD correction is more likely if the patients are <10 years of age.
Trial Registration: Present study was registered in original registration system in Chiba Children’s Hospital. Registration number was 2021-074 and registration date was 14th May 2022.
Acute Biochemical alterations during Phototherapy of Neonatal Icterus: Systematic Review and Meta-analysis
Authors: Chaudhari Hemakshi , Gawli Chandrakant , Kumar Anoop , Patil Chandragouda
Published: January 2023

Purpose
Phototherapy is used in the treatment of neonatal hyperbilirubinemia. There are contravening reports on its its adverse effect. This meta-analysis was conducted to substantiate the impact of phototherapy on the parameters indicating oxidative stress and proinflammatory cytokines.
Methods
The relevant clinical studies were searched on PubMed, Google Scholar, Stanford University High-Wire Press, Clinical trial registry, and on Semantic Scholar published up to 30th July 2022. Newcastle-Ottawa Scale was used to assess the study qualities. The overall estimate was calculated in terms of odds ratio with 95% confidence interval using random effect model. The sensitivity and subgroup analysis were carried out along with the qualitative assessment of the publication bias. All the analysis was carried out using RevMan 5.
Results
Total 1735 participants from 31 pertinent studies were used for the quantitative analysis. The pooled estimates of the phototherapy-exposed group were compared with the control group. Our analysis revealed that phototherapy used in treating neonatal jaundice induced significant oxidative stress and increased the levels of inflammatory cytokines. Overall estimate measure i.e., mean difference was found to be significant [1.39 (0.79 1.99)] for MDA (nmol per ml), [-0.87 (-1.35 -0.39)] for MDA (nmol per litre) [-0.25 (-0.34 -0.15)] for TAC, [-81.68 (-105.50 -57.85)] for TNF-α, and non-significant for TOS and IL-6 i.e [1.36(-2.67 5.39)] and [1.96 (-0.89 4.81)] respectively
Conclusion
Therapeutic exposure to phototherapy in treating neonatal jaundice induces a rise in oxidative stress and inflammatory cytokine levels. The short and long-term clinical outcomes may have clinical significance.
A novel removal of Ni2+ ions from water solutions using dispersive solid-phase extraction method with nano Fe3O4/chitosan-acrylamide hydrogel
Authors: Arvand Morteza Parsayi , Moghimi Ali , Salehi Narges
Published: January 2023

The effluent release containing heavy metals as Ni2+ ions has drastic risks to both the natural environment and human health. In this research, the nano Fe3O4/chitosan-acrylamide hydrogel was prepared as a novel nano sorbent for dispersive solid-phase extraction of Ni2+ ions and applyed in for the water sample solution. The pH, amount and type of elution solvent, the extraction time and etc were optimized for the improving the efficiency of proposed method. Analytical parameters such as concentration factor, the limit of detection and relative standard deviation (%) were achieved as 33.3, 1.25 µg L− 1 and 1.8%, respectively. The capacity in equilibrium sorption was calculated 22.54 mg g− 1. Furthermore, to estimate adsorption mode, the model of Freundlich and Langmuir was fitted to empirical isotherm data. Besides, to check the basic process of the metal adsorption mechanism pseudo-first-order and pseudo-second-order and Roginsky-Zeldovich model were investigated and the resuls were fitted with the pseudo-second-order model. Finally, the nano Fe3O4/chitosan-acrylamide hydrogel exhibited high performance to removal the Ni2+ ions from water sample solution.
The expression of Galectins-8 and its effect on neuroinflammation after intracerebral hemorrhage Names
Authors: Song Jingjing , Lou Jiyu , Jiang Chao , Bai Hongying , Chen Si , Xing Yuanyuan
Published: January 2023

At present, there is no effective treatment for secondary brain injury caused by spontaneous intracerebral hemorrhage (ICH). This study aims to explore new therapeutic targets after ICH. Galectins-8 is a tandem repeat galectin with a unique preference for α2,3-sialylated glycans, and its expression is ubiquitous. Gal − 8 regulates cytokine production, cell adhesion, apoptosis, chemotaxis, endocytosis, differentiation and migration, including immune cells. We used wild-type(WT)C57BL/6J mice and the mice of Galectins-8 gene knockout to establish intracerebral hemorrhage model by collagenase injection and found that Galectins-8 was highly expressed around the hematoma and in the center site of the hematoma after intracerebral hemorrhage. We also found that inhibiting the expression of Galectins-8 or Galectins-8 gene knockout mice may attenuate secondary brain injury following intracerebral hemorrhage by reducing microglia-induced inflammatory responses. Galecectin-8 knockout mice had significantly reduced expression of inflammatory factors, such as TNF-α(P = 0.0353), MCP-1(P = 0.0469), and HMBG1(P = 0.0466). This is in contrast to previous studies that have suggested Galectins-8 as a neuroprotective factor. From this, we draw a conclusion that Galectins-8 played an crucial role in regulating the inflammatory response during intracerebral hemorrhage. Our study highlights Galectins-8 as a potential therapeutic target to protect the brain against secondary brain damage during intracerebral hemorrhage.
Genetic mechanisms and multi-parameter logging identification of low-resistivity oil pay: A case study of the Triassic Chang 6 member, Zhidan area, Ordos Basin, China
Authors: Wang xiaolin , zhu xiaomin , zhang xiaoli
Published: January 2023

Low-resistivity pay have been found throughout the world, the identification and characterization of low-resistivity pay is very challenging and important for the development of oil fields. The genesis of the low-resistivity oil pay is complex, and the logging response characteristics are variable. The weak difference in resistivity between the oil pay and the adjacent water pay makes it difficult to identify kinds of fluids by resistivity log analysis, which reduces the overall exploration benefit of the oilfield. Therefore, it is very important to study the genesis and identification technology of the low-resistivity oil pay. In this paper, we first analyzed the core experimental results such as X-ray diffraction scanning electron microscope, mercury intrusion, phase permeability, nuclear magnetic resonance, physical properties, electric petrophysical experiment, micro-CT technology and rock wettability, etc. Comprehensive analysis of the reservoir characteristics shows that the development of low-resistivity oil pays in the study area is controlled by irreducible water saturation and high gamma ray sandstone. The complicated pore structure and rock hydrophilicity are the factors that lead to the increase of irreducible water saturation. Then, the salinity of formation water and the invasion of drilling fluid also have a certain influence on the change of reservoir resistivity. According to the controlling factors of the low- resistivity oil pay, we extract the sensitive parameters to the logging response, amplify the difference between oil and water pay, and use the AC-RILD, SP-PSP, GR*GR*∆SP-RILD and(RILM-RILD)/RILD—RILD cross-plots, etc. Various methods such as cross-plots method, overlap method and movable water analysis are mutually constrained to identify low-resistivity oil pays. In the case study, the comprehensive application of the above identification flow path can effectively improve the accuracy of fluid recognition step by step. It provides reference for identifying more low-resistivity reservoirs with similar geological conditions.
Experimental and Computational studies on a cricket ball subjected to various seam angles
Authors: Natarajan Rajamurugu , Sambath Yaknesh
Published: January 2023

Investigating the flow pattern over a cricket ball is always intriguing. A comparative study attempt is made in this work with computational work is validated through experimentation. The flow patterns are observed under the velocities of 11m/s, 18m/s, 21m/s, 25m/s, 30m/s and seam angles of 0°,30°,45°,60°& 90° in a subsonic wind tunnel. To study the effect of the seam on a cricket ball with various flow speeds. Both computational and experimentation on cricket ball with different seam angles and velocities were investigated. The results got by the computation has a good validation for the experimental work. The maximum reduction in total drag is found at a 30-degree seam angle and the maximum swing acquired is found at a velocity of 30m/s of the same angle. Through flow visualization, the observed flow patterns also conclude the same.
Fibrocyte: a missing piece in the pathogenesis of fibrous epulis
Authors: Zhu Yifei , Wan Meichen , Gao Peng , Shen Minjuan , Zhu Yina , Hao Jiaxin , Lu Weicheng , Wang Chenyu , Tay Franklin , Ehrlich Hermann , niu Lina , Jiao Kai
Published: January 2023

Objective

To investigate the significant role of fibrocytes in pathogenesis of fibrous epulis.

Material

Human epulis specimens and human peripheral blood mononuclear cells (PBMCs) were used in this study.

Methods

Different subtypes of human fibrous epulides and normal gingival tissue specimens were collected for histological and immunofluorescence analyses. Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human PBMCs were subsequently isolated from peripheral blood to identify the factor that trigger fibrocyte differentiation in vitro.

Results

We demonstrated the presence of circulation-derived fibrocytes in fibrous epulides. These fibrocytes differentiate into myofibroblasts or osteoblasts under the local inflammatory environment in fibrous epulides. TGF-β1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner. The TGF-β1 along with a high calcium and phosphorus extracellular environment stimulates the fibrocytes to differentiate into osteoblasts. The fibrocytes-derived myofibroblasts and osteoblasts are responsible for the fibrogenesis and osteogenesis of fibrous epulides, respectively. The persistent local inflammatory environment drived the differentiation of circulation-derived fibrocytes and drived the recurrence of fibrous epulides.

Conclusions

Fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the recurrence of fibrous epulides.
Tissue resident memory T cells are enriched and dysfunctional in effusion of patients with malignant tumor
Authors: Mao Xueying , Chen Yue , Lu Xiulian , Jin Shuiping , Jiang Piao , Deng Zhangfeng , Zhu Xiaoyun , Cai Qichun , Wu Changyou , Kang Shuangpeng
Published: January 2023

Purpose

Most malignant effusion are secondary to metastases to the pleura or peritoneum and portend poor oncological outcomes. Malignant effusion have different tumor microenvironment from primary tumor, containing a variety of cytokines and immune cells and directly contacting with tumor cells. However, the characteristic of CD4+ T cells and CD8+ T cells in malignant effusion remains unclear.

Methods

Malignant effusion including peritoneal ascites and pleural fluid from thirty-five patients with malignant tumor were collected and compared with matched blood. A detailed characterization of CD4+ T cells and CD8+ T cells in malignant effusion were conducted using flow cytometry and multiple cytokines assay.

Results

The concentration of IL-6 in malignant effusion was significantly higher than in blood. A substantial portion of T cells in malignant effusion were CD69+ and/ or CD103+ Trm cells. Most CD4+T and CD8+T cells in malignant effusion were exhausted T cells which expressed lower levels of cytokines, cytotoxic molecules and markedly higher levels of inhibitory receptor PD-1 compared with in blood.

Conclusion

Our study is the first to identify the presence of Trm cells in malignant effusion and will lay the foundation for future research on anti-tumor immunity of Trm cells in malignant effusion.
Negative impact of the microvascular area to tumor area ratio on the response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer with EGFR mutation
Authors: Anai Moriyasu , Saruwatari Koichi , Imamura Kosuke , Fujino Kosuke , Jodai Takayuki , Sakata Shinya , Iyama Shinji , Tomita Yusuke , Saeki Sho , Ichiyasu Hidenori , Ikeda Koei , Suzuki Minoru , Sakagami Takuro
Published: January 2023

Purpose
Microvessel density plays an essential role in tumor development. However, whether a tumor microenvironment, abundant in microvessels, affects epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) efficacy in patients with non-small cell lung cancer (NSCLC) and EGFR mutations remains unclear. We aimed to investigate the impact of tumor microvessels on EGFR-TKI efficacy in patients with NSCLC and EGFR mutations.
Methods
We retrospectively studied the data of 40 post-operative patients with recurrent NSCLC and EGFR mutations who received EGFR-TKIs as a first-line treatment at Kumamoto University Hospital between January 2010 and February 2021. Tumor sections were retrieved from the tissue registry and analyzed for CD34-positive microvessels using immunohistochemical techniques. The microvascular area ratio (MVR), which is the CD34-positive microvascular area compared to the total tumor area, was measured using StrataQuest. The predictive value of MVR on treatment outcome, assessed via progression-free survival (PFS), was evaluated using a multivariate Cox proportional hazard model.
Results
The median MVR and PFS values of EGFR-TKI were 0.058 (range, 0.013–0.094) and 610 d (range, 102–2807 d), respectively. The median PFS in the high MVR group (≥ 0.058) was significantly shorter than that in the low MVR group (< 0.058; 296 d [95% confidence interval [CI]: 217–374 d] vs. 918 d [95% CI: 279–1556 d], P = 0.002). Multivariate analysis revealed that high MVR was an independent negative predictor of PFS (hazard ratio, 3.21 [95% CI: 1.18–8.76], P = 0.022).
Conclusions
High MVR may critically affect EGFR-TKI resistance in patients with NSCLC and EGFR mutations.
Development of oral simulators with oral diseases and symptoms for nursing oral assessment education
Authors: Haresaku Satoru , Naito Toru , Miyoshi Maki , Aoki Hisae , Monji Mayumi , Nishida Ayako , Kono Yoshinori , Kayama Maiko , Umezaki Yojiro , Kubota Keiko
Published: January 2023

Background: This study aimed to investigate the effectiveness of the newly developed oral simulators with oral diseases and symptoms for nursing students’ oral assessment education to promote their collaboration with oral healthcare professionals after qualification.
Methods: The participants were first-year students (n=105) at a nursing school in Japan. Ten oral simulators with angular cheilitis, missing teeth, dental caries, calculus, periodontitis, hypoglossal induration, food debris, and crust formation were created by a team of dentists. After a 45-minute lecture programme for oral assessment performance with the Oral Health Assessment Tool (OHAT), the ability test with the simulators and the OHAT and the test feedback were conducted in a 30-minute practical programme. To evaluate the effectiveness of the programmes, questionnaire surveys regarding confidence and perceptions of oral assessment performance and ability tests with slides of oral images were conducted at baseline and after the programmes. A Wilcoxon signed-rank test was used to compare their baseline survey results with their postprogramme results.
Results: Ninety-nine students (94.3%) participated in this study. The results of the ability test with the simulators and the OHAT in the practical programme showed that the correct answer rates of assessing tongue, gingiva, present teeth, and oral pain were less than 40%. Their levels of confidence, perception, and ability of oral assessment performance were significantly higher after the programmes than they were at baseline (P<0.05). Their level of confidence in assessing the need for dental referral had the largest increase in scoring level from the lowest scoring level at baseline in the nine postprogramme assessment categories.
Conclusions: This study identified several problems with nursing students’ oral assessment skills and showed that oral assessment education with simulators might be effective in improvingtheir oral assessment confidence, perceptions, and performance.
ZWINT is a cancer prognosis and immune infiltration-related biomarker from pan-cancer analysis
Authors: wang shiqi , Ni Aijun , Chen Youhua , Sun Peili
Published: January 2023

ZWINT plays an important role in regulating the mitotic checkpoint and cell cycle, and is closely associated with tumor proliferation and migration. Recent studies have shown that high ZWINT expression is associated with poor prognosis in patients with lung adenocarcinoma(LUAD) and Glioblastoma (GBM). Previous analyses of ZWINT were limited to a certain type of cancer, but there has not been a systematic pan-cancer study of ZWINT. We used the TCGA (The Cancer Genome Atlas) project and GTEx data (Genotype-Tissue Expression) to analyze ZWINT expression levels and the correlation with cancer survival prognosis. To understand the underlying biological mechanisms of ZWINT and its relevance to immune infiltration, we systematically analyzed ZWINT-associated genetic alterations, immune infiltration and gene enrichment analysis with different bioinformatics methods. Our study showed that ZWINT mRNA expression was elevated in most human tumors and was significantly increased in the early stages of cancer compared to ZWINT expression in normal tissues.ZWINT high expression is significantly correlated with poor prognosis in most tumors. ZWINT is extensively involved in immune infiltration of tumors. Single cell sequencing data showed that ZWINT was significantly associated with cell cycle, DNA repair, DNA damage, and proliferation. Thus, ZWINT expression correlates with prognosis and immune infiltration in tumor patients. ZWINT may be a potential biomarker for prognosis and an important target for tumor immunotherapy.
Assessment of Burnout Status Among Medical Students of Nepal: A Descriptive Cross-Sectional Survey
Authors: Siddiqui Saharoj , Pandey Aashish , Roy Roshan Kumar , Chaudhary Hiramani Prasad , Sah Vivek kumar , Shukla Ambalika , Yasamin Heena
Published: January 2023

Background: Doctors who have been rightly called wounded healers, start experiencing the challenges of this profession right from their student days. Medical students face comparatively higher frequencies of mental morbidities such as depression, anxiety, burnout, and also greater levels of psychological distress. The whole medical curriculum and this field of medicine require immense hard work, sleepless nights, a lot of compassion, and putting in service before self. The students entering medical colleges, who have just taken the first step in this never-ending journey of learning and service begin to experience a lot of challenges and overwhelmed and measurable syllabus, long years of gaining knowledge, and continuous pressure of being up to the mark as it may become a matter of someone’s life or death. Earlier, least discussed as a topic of concern, the mental health of medical professionals is now being talked about, however, enough data is still not available relating to the medical students of Nepal. This study aims to assess burnout among medical students of Nepal.
Methods: A quantitative descriptive study was carried out online among Nepali undergraduate medical students with a cross-sectional design.
Results: Out of 531 students, 72.32% fell in the burnout category. The prevalence of burnout was
76.35% in the first year, and 45.45% in the final year. 67.01% of total males and 78.75% of total females were identified as burnout.
Conclusion: A very high prevalence of burnout was encountered among Nepali undergraduate medical students more commonly in females and first-year students.
Modeling population dynamics of Myzus persicae(Sulzer) and its associated parasitoids in bell pepper in relation to climatic factors
Authors: Sharma Shakshi , Sood Ajay Kumar , Ghongade Dilip Shriram
Published: January 2023

Effect of climatic factors on population build-up of green aphid, Myzus persicae (Sulzer) and associated parasitoids was studied on bell pepper under protected environment over a period of two cropping seasons. Plants were infested artificially by releasing 1, 2, 4 and 8 aphids per plant on 30 days after transplanting. In summer crop, population of apterous aphids at initial infestation levels of release peaked on 42 days after infestation (DAI) with the population of 986.0, 2304.9, 3267.3 and 4380.5 aphids per plant, respectively. Aphid population remained comparatively low in autumn crop, and peaked between 63–70 DAI in different infestation levels. The population levels differed significantly at all infestation levels in summer crop but was on a par at 1 and 2 aphid levels in autumn crop. Alate formation initiated three weeks after release of aphids in both the seasons. Correlation coefficient between aphid population and climatic factors indicated that the temperature favoured build-up of aphid population positively in summer crop, being significant with minimum temperature only (r = 0.5247; p = 0.05), whereas, in autumn crop, both temperature and relative humidity influenced the population buildup negatively, which being significant with minimum temperature and minimum relative humidity. Predictive model using stepwise regression analysis between aphid and abiotic factors revealed that minimum temperature to contribute significantly in influencing the population in both cropping seasons, being less in summer crop (26.6%) as compared to autumn crop where it contributed to the extent of 45.1 per cent. Three hymenopterous parasitoids namely, Aphelinus asychis Walker, Aphidius matricariae Haliday and Aphidius ervi Haliday were found associated with M. persicae. The parasitoid, A. asychis and Aphidius spp. resulted in parasitization varying from 1.0–13.7 and 0.7–61.4 per cent in different aphid infestation levels in summer and autumn crop, respectively. A. asychis showed negative functional response to M. persicae population, whereas Aphidius spp. responded positively. Except maximum temperature all other environmental factors influenced the parasitization positively in both cropping seasons, being significant with minimum relative humidity (r = 0.6990; p = 0.01) in autumn crop only.
Impact of the COVID-19 Pandemic on Urogenital Tuberculosis in Uzbekistan
Authors: Rashidov Z. R. , Parpieva N. N. , Alidzhanov S. K.
Published: January 2023

The objective: to determine the impact of the COVID-19 pandemic on the structure and course of urogenital tuberculosis (UGTB) in Uzbekistan.

Subjects and Methods. A retrospective cohort comparative study of the urogenital tuberculosis structure by clinical data for 2018-2021 was carried out. The data of 2,866 patients with extrapulmonary tuberculosis were analyzed including 1,208 patients with urogenital tuberculosis.

Results. Of the 1,208 patients with urogenital tuberculosis, 327 were registered in 2018, 300 in 2019, 219 in 2020 (the first year of the COVID-19 pandemic), and 362 in 2021. The smallest number of cases registered in 2020 is due to lock-out activities. In 2021, there was a 2-fold increase in the number of patients with co-morbid forms of urogenital tuberculosis versus 2019 (pre-pandemic period). The frequency of detection of Mycobacterium tuberculosis in patients with urogenital tuberculosis in 2021 also increased by 4.3-5 times compared to 2019. The largest number of cases with the co-infection of urogenital tuberculosis and COVID-19 was recorded in 2020 – in 13.2% of identified patients. Concurrent urogenital tuberculosis and encrusting cystitis were observed in 4 (1.1%) patients detected in 2021. The underdetection of urogenital tuberculosis patients in 2020 resulted in the higher proportion of surgeries in 2021.
LncRNA: An Important Regulator of Atherosclerosis
Authors: Ma Yun , He Siqi , Xie Qiao , Tang Zhihan , Jiang Zhisheng
Published: January 2023

Long non-coding RNA (lncRNA) is a kind of biomolecule that can regulate
important life activities such as cell proliferation, apoptosis, differentiation, aging, and
body development. It has been found that lncRNAs are closely related to various diseases.
In cardiovascular diseases, lncRNAs affect the expression level of related genes in
atherosclerotic plaques, which are closely related to endothelial dysfunction, smooth muscle
cell proliferation, macrophage dysfunction, abnormal lipid metabolism, and cellular
autophagy, thus participating in regulating the occurrence and development of AS. In
view of this, investigating the role of lncRNAs in regulating cardiac gene networks on
cardiovascular system diseases has attracted much clinical attention and may be a novel
target for AS therapy. This paper focuses on lncRNAs related to AS, explores the relationship
between lncRNAs and AS, suggests the role of lncRNAs in the prevention and
treatment of AS, and expects the application of more lncRNAs as the marker in the clinical
diagnosis and treatment of AS.
Strategies and Progress Towards the Ideal Orally Active Thrombin Inhibitor
Authors: Rewinkel J.B. M. , Adang A. E. P.
Published: January 2023

Thrombin plays a key role in the control of thrombus formation, for which reason its inhibition has become a target for new antithrombotics. Important issues in the profile of the ideal thrombin inhibitor are: potency, selectivity, oral bioavailability, half-life in the circulatory system and safety. Although many potent direct inhibitors of thrombin have been discovered, most of these inhibitors lack sufficient oral bioavailability. This is often associated with the presence of highly basic functionalities such as guanidine or amidine. These basic functionalities in the P1 moiety are preferred by thrombin and are present in the first generation of thrombin inhibitors. Recently, several orally active direct thrombin inhibitors have been disclosed. Most of these inhibitors originate from leads of the first generation. Two major optimization strategies could be identified to further improve these leads: A: maintain the highly basic P1 moiety and compensate its negative effects, and B: reduce the basicity of the Pi moiety and compensate for the decrease in inhibitory activity. The progress made using these strategies is evaluated. In addition, screening large sets of compounds yielded new structures that provide useful starting points for optimization. The optimization strategy used to convert leads from screening into potent orally active thrombin inhibitors is also be evaluated.
Nanocarrier Based Delivery of Berberine: A Critical Review on Pharmaceutical
and Preclinical Characteristics of the Bioactive
Authors: Hafeez Abdul , Khan Mohd. Jawed , Siddiqui Mohd. Aftab
Published: January 2023

Berberine (BBR) is an isoquinoline alkaloid with several therapeutic properties, including
anti-microbial, anti-diarrhea, anti-viral, anti-inflammatory, antihypertensive, anti-tumor, and
anti-diabetes. However, its low water solubility, low absorption, first-pass metabolism, nontargeting,
and poor bioavailability represent major hurdles to its successful therapeutic applications.
Hence, researchers have attempted to enhance the biological and pharmacological activity of BBR
to overcome its drawbacks by encapsulation of BBR in micro and nano delivery systems. For the
preparation of nanostructured carrier systems of BBR, a range of methods has been developed, and
each method has its benefits and characteristics. This review critically describes different types of
nanocarriers like liposomes, niosomes, ethosomes, nanoemulsions, polymeric nanoparticles, micelles,
dendrimers, and silver and gold nanoparticles that have been used for encapsulation of BBR
for different therapeutic applications. The various pharmaceutical characteristics (size, shape, entrapment
efficiency, zeta potential, drug release, and drug permeation) of these BBR-loaded nanocarriers
have been discussed systematically. Preclinical studies of BBR nanoformulations involving
animal models are also discussed.
Impediment of Cancer by Dietary Plant-derived Alkaloids Through Oxidative Stress: Implications of PI3K/AKT Pathway in Apoptosis, Autophagy, and Ferroptosis
Authors: Manogaran Prasath , Beeraka Narasimha Murthy , Paulraj Raja Singh , Sathiyachandran Perumal , Thammaiappa Mahadevaswamy
Published: January 2023

The adverse toxicities and stemness are two major factors that constrained the usage of therapeutic strategies to target several cancer types. Previous studies explored the efficacy of PI3K/mTOR inhibitors, pan-PI3K inhibitors, and isoform-specific inhibitors against several cancer types, and many of them are currently in clinical trials. The current review described the efficacy of alkaloids derived from dietary plant sources in developing a new anti-cancer to reduce the preva-lence of cancer through the modulation of apoptosis, autophagy, and ferroptosis. We have substan-tially collected the information pertinent to several intracellular pathways, including PI3K signaling, apoptosis, ferroptosis, and autophagy in modulating cancer progression mediated by the plant-derived alkaloids such as daurisoline, dauricine, vasicine, vasicinone, 2-Acetyl-benzylamine, nu-ciferine, liensinine, gramine, and berbamine. These alkaloids exhibit significant anti-cancer poten-tial to inhibit cancer cells by enhancing the intracellular ROS level and modulation of several sig-naling pathways, mainly through the PI3K/AKT pathway. These alkaloids can modulate chemo-therapeutic agents' efficacy in various cancer cells, both in vitro and in vivo models. Overall the fu-tures for the continued use of alkaloids from natural sources against cancer have to be extended, with the implementation of significant enhancements in the chemistry of these alkaloids for targeted delivery. In this review, we have selected major bioactive alkaloids of dietary and medicinal plants origin and discussed the anti-cancer and combinatorial therapeutic implications of these compounds with several FDA-approved drugs against various cancer cells.
A Review of Lipid and Protein Oxidation During Digestion
Authors: Abedinzadeh Solmaz , Torbati Mohammadali , Khezri Sima , Hashempour-Baltork Fataneh , Azadmard-Damirchi Sodeif
Published: January 2023

Lipid and protein oxidation are important reactions in food systems and can degrade
food quality and decrease consumer acceptability. Several factors affect the rate and severity of
these undesirable reactions in food products. However, lipid and protein oxidations can occur in
the digestive system, which is much more complex than in simple food systems. Under digestive
conditions, food matrix and composition are the major factors affecting lipid and protein
oxidations in the body. Lipid and protein oxidation in food matrixes or the digestive system, as
well as product absorption rate, can have serious consequences for human health. This review
aimed to present recent information and discussion on the effects of digestion conditions and
natural and synthetic antioxidants on lipid and protein oxidation.
A Clinical Cognizance of Molecular and Pathological Diagnostic Approach of TNBC
Authors: Balkrishna Acharya , Umar Zango Usman , Kauser Nasir Saima , Arya Vedpriya
Published: January 2023

Genetic, transcriptional, and clinical heterogeneity of disease has remained
to be a prominent obstacle to the development of a targeted therapeutic approach
against TNBC. So far, based on tumor size, lymph node status, and histologic features
TNBC subtypes were stratified. Insights into inter and intratumoral heterogeneity of
TNBC were gained by next-generation sequencing, genomic, transcriptomic,
proteomic, and clinicopathological characterization. To depict tumor response to
neoadjuvant chemotherapy, radiological characterization may also a play significant
role. Biomarkers for subtyping TNBC were highly needed to depict the survival
outcome. This chapter discussed the available and possible molecular and pathological
diagnostic approaches to TNBC. Furthermore, the integration of morphological and
genomic data may emerge as a promising approach for the identification of new
therapeutic and prognostic markers to predict the likely outcome of the disease. This
chapter aims to highlight the molecular and pathological diagnostic approaches to
depict both metastatic and non-metastatic TNBC. 
Evaluating Fate of Emerging Resistance Hitting the Brakes on Conventional Treatment Approach
Authors: Ponnoor Anto Nikhil , Mittal Rashmi
Published: January 2023

The tumor microenvironment of TNBC cells was associated with the
induction of angiogenesis, proliferation, apoptosis inhibition, immune suppression, and
drug resistance. TME creates a niche for the survival and interaction of cancer cells
with surrounding cells. TME promoted epithelial to mesenchymal transition, stemness,
and chemoresistance and ensured the escape of TNBC cells from the chemotherapeutic
and immunological responses. This chapter highlighted the role of cancer stem cells,
hypoxia, lysosomal biomass, tumor-associated macrophages, PTEN, PI3K/Akt/mTOR
pathway, and ABC transporters in inducing resistance against standard therapeutic
regimens. The possible role of miRNA, transcriptional signatures, and tumor-infiltrating lymphocytes as a predictor of chemoresistance was also depicted. The
impact of drug repurposing and combinational therapeutic approach to overcome the
obstacle of chemoresistance have been underlined in this chapter for the treatment of
TNBC. 
Novel Implications of Prognostic Markers to Monitor the Disease: An Overview
Authors: Saxena Rohit , Gupta Ankit , Singh Vikrant , Kumar Sagar , Mittal Rashmi
Published: January 2023

Apart from the absence of targeted therapies, poor prognosis in TNBC has
affected the clinical outcome of the disease and has led to cause high mortality rate
amongst diseased individuals. The discovery of potential biomarkers to determine the
prognostic and predictive value may play a vital role in the development of an effective
therapeutic approach and may improve the OS, DFS, and DMFS. This chapter
highlighted the role of histological subtyping, lymph node status, lymphovascular
invasion, miRNA, Ki-67, TILs, and BRCAness as prognostic markers of diseases.
Nevertheless, patient selection and choice of treatment strategy will greatly impact the
clinical efficacy of these prognostic markers but will remain to be a matter of further
exploration.
Mammographic and Sonographic Findings in Breast Cancer Screening
Authors: Aurora Habiba , Yueniwati Yuyun
Published: January 2023

Breast cancer in the most common malignancy in woman. Screening is very important to identify precancerous lesions. The use of diagnostic imaging is one of the first steps in cancer diagnosis. Mammography is one of detection tool, which able to detect breast abnormality in early stage, while breast sonography is more helpful in cases with dense breast. In this study we compared the finding on mammography and ultrasonography among woman 40 to 60 years undergoing breast cancer screening.

This study included 30 asymptomatic woman aged over 40 years, which have no history of reast cancer. All were assigned to undergo screening by either mammography and ultrasonography. The diagnoses were scored due to ultrasound BI-RADS, the finding from mammography and breast ultrasound were compared to analyze the difference between both examination.

                From the result of mammography and ultrasound were shown that at the same BIRADS scale, different images could be obtained. Further studies are needed to demonstrate the significance of the differences in examination findings on the same BIRADS scale.

 

Keywords: Breast Cancer, Mammography, Screening, Sonography
CT FINDINGS OF THREE GIANT MEDIASTINAL TUMORS IN YOUNG AGE
Authors: Arifah Arifah , Erawati Dini Rachma
Published: January 2023

Background : Mediastinal teratoma and other mediastinal tumors are very challenging to be distinguished from other mediastinal tumors. Mediastinal tumors can be optimally evaluated with computed tomography (CT). In this paper we present three young male patients with similar symptom of chronic chest pain and chronic cough.
Materials and Methods: Conducting a literature review and medical records.
Results : All patients in this case are young age male, below two decades. All chest CT shows giant mass, but they have different enhancing pattern, different amount of solid, cystic, calcification component. To make correct diagnosis of the mediastinal mass is important because of treatment planning difference, surgery or chemoteraphy. The first case shows benign teratoma with characteristic of heterogenous mass with large amount of fat, with presence of solid and calcification component. The second case shows malignant germ cell tumor with feature of heterogenous mass with predominantly solid component and small amount of fat. It also shows metastatic process in lung and bone. The third case shows Hodgkin lymphoma with slight enhanced mass that narrowed pulmonary artery and caused pericardial effusion.
Conclusion: Various features of mediatinal tumors can be distinguished with CT modality.
THE RELATIONSHIP BETWEEN BREAST VOLUME AND BREAST MALIGNANCY IN MAMMOGRAPHY
Authors: Lathifa Jauza Atsil , Yueniwati Yuyun , Fahanani Agwin Fahmi
Published: January 2023

Breast cancer is a major global public health problem and the most common type of cancer. The incidence of cases in Indonesia are about 42.1 per 100.000 population in 2019. There are multiple risk factors that underlie breast cancer malignancy. However, breast volume has not been yet included as a risk factor for breast cancer. The aim of this study is to analyze the association between breast volume and breast malignancy. This study is a cross-sectional study obtaining breast volume and BI-RADS score by performing mammography assessment at dr. Saiful Anwar General Hospital, Malang.
The inclusion criteria were women aged > 40 years and excluded those who have mammography contraindications such as pregnancy and breast-feeding. The parameters for calculating breast volume were the width, height, and compression thickness, and the BI-RADS category (0 – 6) was used to determine the malignancy.  
There is no significant association using the non-parametric analytic test Kruskal Wallis analytic test (p = 0.273 , p < 0.05) and a very weak negative correlation based on the correlation test Spearmanis correlation test (-0.127). There is no association between breast volume and the risk of malignancy based on BI-RADS mammography.
Studi Manajemen Pelaksanaan Konstruksi Bendung Pltm Prafi Kecamatan Warmare Kabupaten Manokwari Provinsi Papua Barat dengan Menggunakan Microsoft Project Manager 2013
Authors: Mandasari Fetri , Marsudi Suwanto , Sholichin Moh.
Published: January 2023

Bendung PLTM Prafi yang terletak di Desa Prafi, Kecamatan Warmare, Kabupaten Monokwari, Propinsi Papua Barat. Kondisi Bendung PTLM Prafi yang masuk dalam klasifikasi very high hazard atau masuk kelas bahaya tinggi sehingga memerlukan tindakan rehabilitasi yang masuk dalam program Dam Operation Improvement and Safety Project (DOISP) dengan tujuan meningkatkan keamanan dan fungsi bendungan besar. Berdasarkan hasil penjadwalan, pelaksanaan konstruksi permanen PLTM Prafi dengan durasi 13,5 bulan didapatkan rencana anggaran biaya sebesar Rp. 49.420.000.000,00 (Empat Puluh Sembilan Milyar Empat Ratus Dua Puluh Juta ibu Rupiah). Setelah dilakukan percepatan jadwal proyek menggunakan alternatif penambahan jam kerja dan alat berat, didapatkan jadwal proyek dengan durasi 12 bulan dengan rencana anggaran biaya sebesar Rp. 47.280.000.000,00 (Empat Puluh TujuhÂ Milyar Dua Ratus Delapan PuluhÂ Juta Rupiah).Sedangkan Percepatan jadwal proyek dengan alternatif penambahan alat berat dengan durasi 10 bulan dengan rencana anggaran biaya Rp. 49.100.000.000,00 (Empat Puluh Sembilan Milyar Seratus Juta Rupiah).
Analisa Pengaruh Penggunaan Mulsa Jerami Padi Dalam Mengontrol Erosi Tanah Menggunakan Rainfall Simulator
Authors: Aji Azra Lindu , Haribowo Riyanto , Fidari Jadfan Sidqi
Published: January 2023

Penginstalasian mulsa jerami padi di lahan pertanian adalah salah satu metode yang digunakan dalam mengontrol erosi tanah. Tujuan dari penelitian ini adalah untuk menentukan efektivitas mulsa jerami padi dalam mengurangi kehilangan tanah sebelum memasuki sungai. Tanah uji yang digunakan berasal dari Desa Sumber Brantas, Kecamatan Bumiaji, Kota Batu. Studi ini menggunakan Rainfall Simulator Armfield S12 â€“ Advanced Environmental Hydrology System, dengan pemodelan hujan sebesar 1,7 dan 1 liter/menit. Dalam studi ini, lahan dengan mulsa jerami dibandingkan dengan lahan dengan tanpa mulsa jerami padi. Kemiringan lahan disesuaikan dengan kondisi area studi landai (9%) dan curam (15%). Metode ANOVA Tiga Arah digunakan dalam analisa statistik. Berdasarkan hasil analisa, diketahui bahwa mulsa jerami padi efektif mengurangi total sedimen yang masuk ke sungai dalam jumlah yang besar. Hasil analisa ANOVA juga menunjukanÂ bahwaÂ nilai signifikansi dari lahan dengan mulsa jerami padi dibandingkan dengan lahan tanpa mulsa jerami padi bernilai 0. Hasil ini menunjukkan bahwa penggunaan mulsa jerami padi mengurangi total sedimen sekitar 63%.
Perencanaan Sistem Distribusi Air Bersih di Desa Watukebo, Kecamatan Wongsorejo, Kabupaten Banyuwangi
Authors: Cahyani Sylvia Regita , Haribowo Riyanto , Sholichin Mohammad
Published: January 2023

Desa Watukebo merupakan salah satu desa yang terletak di Kecamatan Wongsorejo, Kabupaten Banyuwangi dengan permasalahan krisis air. Waduk Bajulmati sebagai wadah penyimpanan air cadangan direncanakan menjadi solusi dalam menjawab permasalahan krisis air yang terjadi pada Desa Watukebo. Diperlukan adanya sarana dan prasarana untuk merealisasikan solusi tersebut dengan merencanakan sistem distribusi air bersih di Desa Watukebo berdasarkan aspek hidraulik, kualitas air, dan ekonomi dengan menggunakan bantuan Software WateraCAD V8i. Jaringan perpipaan direncanakan menggunakan Pipa GI pada jalur transmisiÂ dan Â pipa HDPE serta PVC pada jalur distribusi. Mengacu pada Permen PUPR No. 18/PRT/M/2007 hasil analisa berdasarkan aspek hidraulik dan kualitas air sudah sesuai dengan standart kriteria yang ada. Hasil studi perencanaan ini yaitu nilai kecepatan berkisar antara 0,1 â€“ 1,56 m/s, nilai headloss gradient berkisar antara 0,16 â€“ 14,96 m/km, nilai tekanan berkisar antara 0,84 â€“ 5,32 atm, dan nilai sisa klorin berkisar antara 0,3 â€“ 0,4 mg/l. Perhitungan rencana biaya anggaran dilakukan secara manual dengan mengacu pada Permen PUPR No 28/PRT/M/2016. Total Rencana Anggaran Biaya (RAB) yang diperoleh adalah sebesar Rp 2.965.300.000.
Analisa Erosi Dan Sedimentasi Waduk Parangjoho Kabupaten Wonogiri Menggunakan Metode MUSLE Dan Peningkatan Kapasitas Tampungan Waduk
Authors: Palupi Gema Anggun , Sholichin Mohammad , Sisinggih Dian
Published: January 2023

Daerah aliran sungai sebagai daerah tangkapan air sehingga rentan terhadap masalah erosi dan sedimentasi.Sedimen akan terus meningkat seiring dengan bertambahnya jumlah erosi Penelitian ini memilih lokasi di Waduk Parangjoho yang terletak di Kabupaten Wonogiri, Jawa Tengah.Tujuan penilitian ini adalah memperkirakan nilai pendugaan erosi dan sedimentasi menggunakan metode Modified Universal Soil Loss Equation ( MUSLE ) di DAS Parangjoho, data yang diperlukan yaitu, data hujan harian maksimum tahun 2001-2020 yang digunakan untuk menghitung nilai debit banjir rancangan yang dapat digunakan perhitungan nilai indeks erosivitas limpasan permukaan, kemudian peta jenis tanah untuk mendapatkan faktor ( K), peta kemiringan lereng untuk faktor LS, peta tata guna lahan untuk faktor CP, dari data tersebut didapatkan besar laju erosi dan sedimentasi sebesar 54.898,14 ton/tahun, nilai laju sedimentasi metode MUSLE tidak memerlukan SDR sehingga nilai laju sedimentasi sama dengan nilai total erosi pada DAS Parangjoho. Setelah didapatkan besar laju sedimentasi dan berdasarkan data bathimetri bahwa usia guna waduk Parangjoho telah terlampaui maka perlunya melakukan penanganan dengan metode vegetatif dan mekanis. Setelah itu melakukan perhitungan kembali setelah adanya penanganan di Waduk Parangjoho, dan didapatkan sedimen setelah adanya skenario penanganan sebesar 13.015,33 ton/tahun dan terdapat volume tambahan sebesar 27.417 m3 sehingga usia guna bertambah menjadi 11 tahun.
Penilaian Indeks Kinerja Fisik Jaringan Irigasi pada Daerah Irigasi Bangkok Kabupaten Kediri dengan Menggunakan ePAKSI
Authors: Nor Achmad Sholahudin , Wahyuni Sri , Prasetyorini Linda
Published: January 2023

Bangkok Irrigation Area has a service area of 307.58 ha and is located in Kandangan District, Kediri Regency, East Java. In an effort to fulfill the need for proper water building infrastructure for agricultural purposes, good irrigation infrastructure is needed. According to data from the Kediri Regency PU Office, the Bangkok Irrigation Area has suffered damage in recent years. This study uses a comparison of two methods to determine the physical performance index of irrigation networks, namely the PU method and the ePAKSI method. With the PU method, a physical performance index of 60.16% was obtained while the ePAKSI method was 63.40% so that the irrigation network was declared in a moderately damaged condition and periodic maintenance was needed in a repair nature. The estimated cost of repairing buildings with the most severe damage, namely the B.BK.4 Tapping Building and the R.BK.4.Ka Tertiary Channel, is Rp. 230,000,000.00.