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Acute myeloid leukaemia (AML) is the forefront disorder of the bone marrow among others that disrupt the normal production of blood cells and platelets. The bone marrow microenvironment or the bone marrow niche (BM niche) that orchestrates the proliferation and survival of Leukaemic stem cells (LSC) is the reason for relapse after complete remission and also chemotherapy drug resistance. As for most cancers oxidative phosphorylation, a fundamental mitochondrial process of energy production, is under focus for the treatment of AML and a novel strategy of targeting heat shock proteins appears as a promising route for further research.

A survey was conducted in the agricultural farms in Dhulikhel Municipality, mid-hill, Kavre, Nepal aiming at assessing the status of agrobiodiversity with the purpose of understanding its role in food security taking altogether 133 farming households scattered in several settlements with lowland, upland, and home garden being the general agricultural land use systems. Biodiversity index: Shannon-Wiener Index was used to assess diversity of plant. The main purpose was to assess the farm agrobiodiversity and to find out whether biodiversity level has a direct link to household food self-sufficiency. For descriptive analysis frequency, percentage, mean and standard errors were used. In the case of inferential statistics independent sample t - test and binary logistic was used to find the odd ratio of practicing home garden. The result showed that the average landholding size was 0.66 ha/household with 0.37 ha, 0.3 ha, and 0.06 ha being upland, low land, and home garden, respectively. A total of 136 plant species were documented out of which 74 were the effective number of species in the study area. Among the used plants, fodder shared 27% of the total plant diversity followed by fruit (21%), vegetable (19%), medicinal plants (8%), pulses (8%), spices (7%), oilseeds (5%) and cereals (5%). Similarly, the mean livestock unit (LSU) was 2.65. The overall Shannon-Wiener Index was 4.30 indicating high diversity of species and 87.7% of the species were evenly distributed. The Index was higher for vegetable (3.11) followed by fruits (2.9) and fodder (2.85). Higher diversity was found in fodder trees in lowlands whereas vegetable species were more diverse in upland and home garden. Similarly, the Index was 4.29 in the upland whereas it was 4.078 in the home garden followed by 3.13 in the lowland. The evenness was 0.899, 0.87, and 0.74 in upland, home garden and lowland, respectively. Higher species diversity revealed that the site was rich in agrobiodiversity. A significant positive correlation (0.22) was observed between Shannon-Wiener Index and farming years. Similarly, positive correlation (0.33) was found between an increase in the level of agrobiodiversity and food self-sufficiency. The result demonstrated that increasing crop diversity increases the household’s ability towards food sufficiency implying the need for the formulation and implementation of efficient policy to conserve the agrobiodiversity at municipality as well as national levels.

In administrative and economic science, factor analysis models are essential for their explanatory capacity of institutional responses to risk events. The objective of this document was to contrast a model that explains the emergence of corporate governance dimensions in the face of the pandemic. An exploratory study was carried out based on a systematic review of the literature from 2020 to 2023, considering the search by keywords in Google scholar and Microsoft academic, as well as the judges from a public university in the center of Mexico. The results show that corporate identity explains the university’s response to the pandemic. In relation to the state of the art, the scope and limits of the model are discussed in other proposals.

mRNA drugs are synthesized using cell-free systems without complex and stringent manufacturing processes, which makes their preparation simple, efficient, and economical. Over the past few years, mRNAs encoding antibodies have been one of the research frontiers of antibody drug development. In cancer immunotherapy, mRNAs encoding immune checkpoint antibodies may be advantageous regarding antibody persistence and durability of the anti-tumor immune response of patients. In our previous study, a candidate antibody—AET2010—targeting the novel immune checkpoint TIGIT was reported. Its anti-tumor activity was also investigated using adoptive transfer of NK-92MI cells in a xenograft mouse model, but the limitations of the model did not facilitate precise evaluation. In the present study, we further investigated the therapeutic potential of AET2010 for cancer in TIGIT-humanized BALB/c mice. Next, we explored the design, synthesis, and optimization of mRNAs encoding AET2010 and ultimately obtained a candidate mRNA (mRNA-BU) with favorable in vitro and in vivo expression levels of active AET2010. Particularly, lipid-nanoparticle-encapsulated mRNA-BU delivered to mice produced AET2010 with significantly higher peak concentration and expression duration than an equivalent dose of original AET2010. This study provides a sound basis for developing novel drugs targeting TIGIT.

There is an urgent need for predictive preclinical models to enhance the success rate of clinical trial outcomes. One of the main reasons for drug attrition is the lack of translational models, methods using human cells are particularly in the spotlight of regulatory bodies as they offer an alternative to in vivo studies and have the potential to improve the translational of preclinical trials. Organs-on-Chips (OoCs) are sensible candidates to reduce the cost and the ethical burden of animal models while accelerating and de-risking drug development. The innovation of such systems is based on both the increased relevance of the cells used and the ability to build precise, yet physiologically relevant, complex architectures. The use of microfluidic technologies with human induced pluripotent stem cells (hiPSCs) opens new routes to create relevant in vitro approaches as they will soon be able to reproduce clinical characteristics of donors or specific populations. The adoption of OoC models by pharmaceutical industries, and in fine by regulatory agencies, still requires: (i) establishing standardized, reproducible, robust, and replicable cell culture protocols with specific validation and characterization criteria, (ii) evidence that the technology predicts human responses, thus allowing to contribute efficiently and reliably to clinical trials success of novel therapeutics, and (iii) evidence that the models refine and reduce animal testing without compromising with the quality and the pertinence of the data generated.

Gliomas are known to be one of the most grievous malignant central nervous system (CNS) tumors and have a high mortality rate with a low survival rate severe disability and increase risk of recurrence. Aim of his study is to determine the diagnostic accuracy of apparent diffusion coefficient (ADC) in differentiating low-grade and high-grade gliomas, taking histopathology as the gold standard. It is a Cross-sectional validation study conducted at the Armed Forces Institute of Radiology and Imaging, (AFIRI) Rawalpindi, Pakistan from 28th February 2022 to 27th August 2022.Materials and methods: A total of 215 patients with focal brain lesions of age 25-65 years of either gender were included. Patients with a cardiac pacemaker, breastfeeding females, de-myelinating lesions and malignant infiltrates, and renal failure were excluded. Then diffusion-weighted magnetic resonance imaging was performed on each patient by using a 1.5 Tesla MR system. The area of greatest diffusion restriction (lowest ADC) within the solid tumor component was identified while avoiding areas of peritumoral edema. Results of ADC were interpreted by a consultant radiologist (at least 5 years of post-fellowship experience) for high or low-grade glioma. After this, each patient has undergone a biopsy in the concerned ward, and histopathology results were compared with ADC findings. Results: Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of apparent diffusion coefficient (ADC) in differentiating low- and high-grade gliomas, taking histopathology as the gold standard was 93.65%, 87.64%, 91.47%, 90.70% and 91.16% respectively. Conclusion: This study concluded that apparent diffusion coefficient (ADC) is the non-invasive modality of choice with high diagnostic accuracy in differentiating low- and high-grade gliomas.

Therapies using autologous serum and platelet lysate have shown promise among blood and biological products in the treatment of various diseases. The autologous serum has been shown to be a superior alternative to traditional eye drops in treating eye diseases in ophthalmology. Platelet lysate (PL) has recently been considered a more interesting alternative for the treatment of multiple tissues, as it does not have the unfavorable reactions seen with traditional platelet-rich plasma (PRP), making it a valuable blood derivative for use in ocular therapy. There is no definitive comparison in veterinary medicine between PL and autologous serum in terms of the content of Transforming Growth Factor beta 1 (TGF-1), which is known to have chemotactic, mitogenic, matrix formation, and angiogenesis effects on tissues, and beneficial proteins in ocular tissue. This study aimed to estimate the concentrations of TGF-1, total protein, and albumin, as well as autologous serum and platelet lysate, in horses over an 8-day storage period at temperatures of 4 °C and 37 °C.To produce autologous serum, 63 ml of blood was collected from each animal in seven 9 ml tubes without anticoagulant. For platelet lysate, 180 ml of blood was collected in 50 tubes of 3.6 ml with 3.2% sodium citrate. The most significant findings were the positive relationship between the baseline platelet count in the blood and the final platelet concentration in PRP. Specifically, we found a correlation (R = 0.9) with a p - value of 0.005 between the average baseline platelet level of seven animals and their corresponding PRP results, both on an individual level and as a group. Additionally, there was a correlation between growth factor concentration and PRP platelets, with the highest growth factor concentration in PL. The temperature storage group exhibited higher concentrations of total protein and serum albumin, as well as the maximum amount of growth factor for both products at a temperature of 37 °C.

Most underwater explosions show characteristics of a bubble pulse and reverberation effects. To specifically identify the cause of an underwater explosion, it is most important to find a bubble pulse and reverberation effects using spectral and cepstral analyses. For a very shallow underwater explosion, spectral analysis is preferable to cepstral analysis. Time-domain analyses show bubble pulses as well as positive polarities of the first P-wave arrivals on the vertical component, and frequency-domain spectral analyses also clearly reveal the bubble pulse and reverberation effects. This study includes comparative studies including a Russian underwater nuclear explosion and US Navy shock trials. The ROKS Cheonan sinking was a shallow underwater explosion that occurred near the surface showing a bubble jet characteristic resulting in splitting the ship into two pieces including a bubble pulse and reverberation effects. The findings of a bubble jet and a toroidal bubble deformation including a bubble pulse are highlighted for a shallow underwater explosion in this study. The ROKS Cheonan sinking took place off the Baengnyeong Island in the Yellow Sea of the Korean Peninsula at a depth of about 8 m in the sea depth of 44 m on March 26, 2010. The explosive charge weight was estimated at 136 kg TNT which is equivalent to one of the abandoned land control mines (LCM) that were deployed near the Northern Limited Lines (NLL) in the Yellow Sea in the late 1970s.

To reduce bleaching side effects, the use of low concentrations of Hydrogen Peroxide (HP) agents associated with hybrid light (violet LED/Diode Laser) has gained interest. Case report: The aim of this report is to describe a case of a 16-year-old patient that presented a complaint related to the color of his teeth and a maxillary midline diastema. In-office bleaching with 6% HP associated with hybrid light (violet LED/Diode Laser) was performed. The bleaching gel was applied once on the teeth and light-activated for 1 minute (15 times) followed by 1min intervals (15 times) with a total bleaching time of 30 minutes. After the bleaching procedure, the teeth were polished and the desensitizer was applied for 4 minutes. Two bleaching sessions were performed at a 1-week interval. The diastema was closed with direct resin composite restorations without any tooth preparation. The conventional 3-step bonding agent was used and A1 dentin shade and B1 enamel shade were used followed by polishing discs. At 3-year recall, discoloration and fractures were not found on the the teeth or restorations and patient was completely satisfied. Conclusion: the conservative and safe option of bleaching with a low-concentrated HP gel associated with violet LED light is an interesting option for young patients and presents longevity over time.

Dentistry is an ever-evolving field that has seen significant advances in recent years. This article sheds light on some of the current and emerging trends in oral health care, including digital dentistry, regenerative medicine, and the use of lasers. For example, digital dentistry involves the use of computer-aided design and manufacturing technology, which enables more accurate and efficient production of dental devices. On the other hand, regenerative medicine and nanoDentistry can be considered promising area that combines the use of stem cells, growth factors, biomaterials, and nanotechnology to regenerate damaged tissue and improve treatment outcomes. Lasers are increasingly being used in dentistry for a range of applications, including the treatment of gum disease and teeth whitening. Other developing technologies such as 3D printing and artificial intelligence are also being increasingly incorporated into dentistry, providing improved treatment options for our patients. Last yet definitely would/will not least, controlled drug delivery systems are being developed to deliver drugs to specific target sites in a localized and sustained manner, reducing the risk of adverse effects. Currently, these emerging trends are transforming the landscape of odontology and beyond. Hence, in this mini-Review, we explore such trends in oro-dental and cranio-maxillo-facial indications to highlight the potential benefits, advancements, and opportunities of applications for improved patient care.

In 2005 we reported for the first time on a chemical route aiming to synthesize stable magnetic carbon/graphite. By using the Nuclear Magnetic Resonance (NMR) technique we have verified that its magnetism is an intrinsic property of this synthesized material and not originated from ferromagnetic impurities of any kind. Through direct measurement of the local magnetic field using Carbon-13, we have concluded that its magnetism originated from defects in the structure. From its biocompatibility, we have been working on the use of magnetic carbon/graphite to deliver many compounds aiming to fight different diseases. Despite all the scientific and technological advances of the present day, cancer is a multifactorial and difficult-to-treat disease, killing hundreds of thousands of people a year worldwide. Therefore, the development of a new and efficient drug delivery system to fight cancer – among other diseases - is as important as the discovery of a novel active molecule. In this review of our own work, we show the drug delivery system named MAGUS® (an acronym for Magnetic Graphite Universal System) we have built based on nanostructured magnetic carbon/graphite. This is an innovative and promising system composed of a biocompatible nanostructured particle of magnetic carbon/graphite functionalized with different molecules and materials. MAGUS®, depending on what we link to its structure, is so versatile and can be used to detect a wide range of specimens, from tumors and cancers to chemical and biological agents used as non-conventional weapons. That is why we call it universal. In the present work, MAGUS® will be acting as a biosensor, where the magnetic carbon/graphite is functionalized with radioactive particles of Iodine-131 and antibodies of different types of cancer. Then, by focusing on both the antigen-antibody interaction and the spatial guiding through an external magnetic field we are providing our drug delivery system a double way to detect and reach just the target. Based on these strategies, the functionalized magnetic carbon/graphite will reach only the neoplasm and not the surrounding healthy cells around. In a general view, it means that we are giving specificity to the MAGUS® drug delivery system as a pioneering and effective way to detect and treat cancers. We are also working on this unprecedented and efficient drug delivery system using the principles of Boron Neutron Capture Therapy (BNCT) with Boron-10 instead of Iodine-131. BNCT technique uses neutrons as the external source and is frequently employed to treat specific tumors that are radio resistant or very difficult to kill using conventional radiation therapy. In summary, we show here for the first time that our Magnetic Graphite Universal System associated with nuclear techniques can be successfully used as a biosensor to detect and fight cancers and tumors with powerful features that conventional delivery drug systems and other treatments do not have at all.

Systemic sclerosis sine scleroderma is a rare subset of systemic sclerosis with isolated organ involvement. Scleroderma renal crisis is a severe manifestation of systemic sclerosis characterized by malignant hypertension, oligo/anuric renal failure, and thrombotic microangiopathy. We present a case of a 55-year-old male with uncontrolled hypertension who presented with hematospermia and was found to have acute renal failure, microangiopathic hemolytic anemia, concerning thrombotic microangiopathy. Empiric management for thrombotic thrombocytopenic purpura (TTP) with plasma exchange and corticosteroids yielded a paradoxical response, ultimately leading to the diagnosis of systemic sclerosis sine scleroderma presenting as scleroderma renal crisis (SRC) after serological confirmation. Given the morbidity and mortality associated with scleroderma renal crisis, it should be increasingly considered as a differential for thrombotic microangiopathy even without outward manifestations of systemic sclerosis. Additionally, the empiric management of TTP can include the use of corticosteroids which can exacerbate SRC, an early clinical clue in the diagnosis of this disease.

Background: Osteopoikilosis (OPK) is a rare osteosclerotic dysplasia. It is usually asymptomatic and diagnosis is made incidentally by radiographic findings. It has a unique radiographic presentation with multiple small, well-defined, circular, or ovoid radiodensities which are distributed symmetrically in the epiphysis and metaphysis of long bones.Aim of the work: In this case report, a 38-year-old man with mild joint discomfort was diagnosed with OPK according to his radiographic findings and literature review.Conclusion: It is important to diagnose OPK and to distinguish it from other medical conditions to calm the patient and to reduce unnecessary investigation.

Coronary heart disease (CHD) seriously endangers human health, and there are obvious gender differences in incidence rate and prognosis, which are related to the evident differences in anatomical structure, physiological characteristics, and wall shear stress between males and females. In recent years, cardiac rehabilitation has been proven to be safe and effective in controlling the progression and improving the prognosis of CHD. Thereinto, exercise therapy is the central link of cardiac rehabilitation. Exercise can significantly affect vascular endothelial function by regulating wall shear stress. Based on previous research, this paper will briefly review the influence of exercise on wall shear stress in male and female patients with CHD, in order to provide a reference for formulating personalized cardiac rehabilitation programs and further improve the prognosis of CHD.

Canal cleaning is a routine activity on the canals diverted from the Kabul River. As a result, thousands of tons of sediment are removed as sludge and flushed back into the Kabul River. In Peshawar city, most people use this sediment as a soil conditioner in lawns. But the farmers are hesitant to apply it in agricultural fields. It is perceived that the sediment may be rich in heavy metal contents and, if used as a soil conditioner, may contaminate the food chain. To unveil the facts, this study was conducted with the aim of analyzing sediment samples for selected heavy metals and their uptake and accumulation in different parts of the wheat plant. For this purpose, the sediment collected from Warsak Gravity Canal (WGC) was analyzed for total essential heavy metals including iron (Fe), copper (Cu), cobalt (Co), manganese (Mn), and Zinc (Zn). Wheat crop was grown in four different pots consisting of pure soil, pure sediment, and two amendments i.e. soil mixed with 25% and 50% sediments. In comparison to sediment, the soil samples were high in copper, cobalt, and Zinc concentration. The concentration of iron and manganese was comparatively high in pure sediment but within permissible limits. The heavy metals uptake by the wheat crop was also within the permissible limits. The highest accumulation of copper, iron, and Zinc was observed in the roots of wheat plants. The highest value of cobalt was observed in the seed (0.407 mg Kg-1), which was within the safe range. Therefore, it is concluded that the sediment of the Kabul River canal cannot be considered a source of pollution in terms of heavy metals and can be used as a soil conditioner.

The ability to live things to transfer their genetic heritage to future generations in a healthy way forms the basis of the science of reproduction. In this sense, understanding the structure and functions of the sperm cell, which is one of the sexual cells, is one of the important issues that should be emphasized. Methods such as omics, genomics, proteomics, and metabolomics, which have been found in research in recent years, are also used to evaluate the functions of the sperm cell.

Background: Pregnant individuals with early cervical dilation have a high risk for preterm birth. The authors encountered cases where cervical dilation increased after anesthesia administration for a cerclage. Objective: The primary objective was to assess if a change in cervical dilation after anesthesia administration for a cerclage was associated with a shorter latency to delivery. Study design: This was a retrospective chart review of pregnancies from January 1, 2011, to December 31, 2021, who had a cerclage and delivered at our institution. Maternal demographics, obstetrical history, operative details, and delivery information were collected. Multi-fetal gestations, un-indicated cerclages, and abdominal cerclages were excluded. The primary outcome was the difference in cervical dilation between the office and the operating room after spinal anesthesia administration. A multivariable regression was performed. Results: A total of 183 pregnancies were included. The mean gestational age at cerclage placement was 18 weeks (STDEV 3.6). Twenty-nine percent of patients (53/183) were more dilated in the operating room compared to the office The latency between cerclage and delivery was not different if there was a cervical change between these settings (p = 0.655). There was an increased risk for preterm delivery with dilation in the office (OR 1.01, CI 1.01 to 2.5), but not with dilation in the operating room (OR 1.4, CI 0.9 to 2.0). Conclusion: Cervical dilation between the office and the operating room is different. Pregnancies with more dilation delivered at earlier gestations. However, a change in dilation between the office and the operating room was not associated with a shorter latency. 

The gold standard for advanced-stage ovarian cancer surgery entails exploration via a midline vertical laparotomy. Studies have shown that minimally invasive surgery (MIS) can be a safe and effective method for the surgical management of early ovarian cancer. In some cases, MIS can also be selectively used for cytoreductive surgery in cases with advanced-stage ovarian cancer. The robotic platform has the potential to provide similar outcomes to the laparotomy-based standard of care in advanced complex surgery while accelerating recovery, minimizing morbidity, and reducing perioperative complications. The primary objective of this study was to evaluate surgical and perioperative outcomes in patients with advanced ovarian carcinoma who underwent robotic-assisted cytoreduction. A chart review of a nonselected consecutive series of all patients undergoing surgical management of advanced ovarian cancer between 7/1/2017 and 12/31/2021 was conducted. All patients that were diagnosed with Stage III to IV ovarian cancer between the timeframe underwent robotic-assisted cytoreductive surgery at two urban community teaching hospitals in Los Angeles. Twenty-five patients were identified and included in this study. All surgeries were performed by a single surgeon. Optimal or complete CRS was achieved in 96% of the patients (24 of 25 cases). Seven (28%) underwent primary cytoreduction (PCRS) and 18 (72%) underwent interval cytoreduction (ICRS). The estimated median blood loss was 100 mL (25-500 mL), the median operative time was 5.9 hours (3.1-10.5 hours), and the conversion rate to open laparotomy was 0%. There were no intraoperative complications and the readmission rate within 30 days was 4% (1 patient) for ileus, which was managed conservatively. Currently, 64% of the patients in the case series remain alive. The median survival has not been reached. The median follow-up is 4.08 years. Results presented from this nonselected, consecutive case series illustrate how a minimally invasive robotic approach can be safely used in place of the standard exploratory laparotomy for ovarian cytoreduction.

In this study, the authors systematically examined the anatomical and biomechanical properties of the ligaments in the normal rat knee. These biomechanical data will facilitate the use of the rat knee model for future studies of knee ligament injury, repair, and reconstruction. Fifty-six fresh cadaver male Sprague-Dawley rats, aged 16 weeks, were used for this study, with 48 rats for biomechanical testing and 8 for micro-CT and histological evaluation. Our findings suggest that the gross anatomy of the rat knee joint and ligaments is very similar to humans despite some minor differences and features unique to the rat knee. The patella tendon and ACL are the two strongest soft tissue structures in the rat knee joint, with the highest failure force and stiffness, and both play a role in the anterior stability of the knee. In comparison, the failure force and stiffness of the LCL is half of the MCL, suggesting that other structures, such as the popliteal tendon, may play some role in lateral knee stabilization besides the LCL. In addition, our data suggest that anterior knee stability was improved after ACL reconstruction, but was not fully restored to intact ACL function. In conclusion, our study indicates the anatomical and biomechanical properties of the knee joint and ligaments of rat knees. Then we could confirm a reproducible and realistic rat model of knee ligaments like the clinical cases, and provide a basis for the study of knee ligament biology that simulates techniques used in humans.

Study design: Descriptive study.Background: Many risk factors contributing to ankle sprains have been studied in medical literature with coordination and balance being two of the major endogenous factors described. These are influenced by lateralization – a developmental and adaptive ability determined by the asymmetrical construction of the human brain, with cross-laterality referring to mixed limb dominance.Objectives: To determine whether cross lateralization is a risk factor for the severity of ligamentous injuries in ankle sprains since no data is yet available on such correlation. Methods: Two hundred forty-four patients with acute ankle sprains (136 men and 108 women) were prospectively evaluated between April 2006 and March 2009. The mean age was 30 (ranging from 18 to 76). Clinical and ultrasonographic examinations were performed on the study subjects. Laterality was then assessed by the Coren questionnaire and the AOFAS score was calculated. Patients with syndesmotic injuries and fractures were excluded from the study. Those qualified were divided into straight and crossed groups, according to their laterality type. Results: One hundred forty-four patients displayed straight lateralization, while cross-laterality was found in 100 subjects. Patients in the crossed group experienced more multi-ligamentous injuries than those in the straight group (p = 0.02). Following trauma, a higher AOFAS score was attributed to subjects that displayed a straight lateralization pattern, in comparison to subjects presenting with crossed laterality (p = 0.04).Conclusion: Crossed lateralization is associated with higher severity of ligament injuries in ankle sprains and may be considered a risk factor for calcaneofibular ligament injuries.