Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of ERCC1 and Hormonal Receptor Expression in Ovarian Cancer.

Background & Objectives : Ovarian carcinoma usually has a relatively poor prognosis. A rational approach to identify patients, who are likely to benefit from therapy, is urgently needed. Excision repair cross-complementation group 1 enzyme (ERCC1) has been proposed as a molecular predictor of clinical resistance to platinum-based chemotherapy. Steroid hormone receptors are important determinants of prognosis and predictive behavior in tumor tissues of several origins. The present study aimed to investigate the expression profile of ERCC1, ER & AR in patients with Ovarian carcinoma and their association with patient outcome. Methods : This is a prospective study which included 77 patients with ovarian carcinoma who were treated with platinum based chemotherapy at the National Cancer Institute (NCI) in Egypt during the period 7/2016- 7/2018. We evaluated the expression of ER, AR, and Excision repair cross-complementation group 1 enzyme (ERCC1) by immunohistochemistry. Expression profiles were compared to clinical, histologic and prognostic factors, the clinical outcome and survival. All patients received platinum containing chemotherapy regimen. Result : Of the 77 patients with ovarian cancer, 66.2 % (51/77) were ERCC1-positive, 49.4 % (38/77) were AR positive & 75.3 % (58/77) were ER positive. Platinum resistance was found in eight of the tumors with positive ERCC1 protein expression compared with two among the patients with negative tumor staining for ERCC1 (P = 0.643). There was significant association between ER & AR expression and pathological subtypes (p = 0.004, 0.007) respectively. There were no significant association between ER, AR& ERCC1 expression and PFS (P = 0.447,P = 0.162, P = 0.508 respectively) or OS (P = 0.781, P = 0.569, P = 0.381 respectively). Based on Cox proportional hazards regression analysis ERCC1, ER &AR were not independent factors affecting the prognosis of patients with ovarian carcinoma. Conclusion : These results demonstrate that positive ERCC1 expression is not associated with clinical resistance to platinum-based chemotherapy, ERCC1, AR& ER expression are not independent factors affecting the prognosis of patients with epithelial ovarian tumors and not associated with survival benefits. J. Med. Invest. 67 : 391-398, August, 2020.
Review and Consensus on Pharmacogenomic Testing in Psychiatry

Abstract The implementation of pharmacogenomic (PGx) testing in psychiatry remains modest, in part due to divergent perceptions of the quality and completeness of the evidence base and diverse perspectives on the clinical utility of PGx testing among psychiatrists and other healthcare providers. Recognizing the current lack of consensus within the field, the International Society of Psychiatric Genetics assembled a group of experts to conduct a narrative synthesis of the PGx literature, prescribing guidelines, and product labels related to psychotropic medications as well as the key considerations and limitations related to the use of PGx testing in psychiatry. The group concluded that to inform medication selection and dosing of several commonly-used antidepressant and antipsychotic medications, current published evidence, prescribing guidelines, and product labels support the use of PGx testing for 2 cytochrome P450 genes (CYP2D6, CYP2C19). In addition, the evidence supports testing for human leukocyte antigen genes when using the mood stabilizers carbamazepine (HLA-A and HLA-B), oxcarbazepine (HLA-B), and phenytoin (CYP2C9, HLA-B). For valproate, screening for variants in certain genes (POLG, OTC, CSP1) is recommended when a mitochondrial disorder or a urea cycle disorder is suspected. Although barriers to implementing PGx testing remain to be fully resolved, the current trajectory of discovery and innovation in the field suggests these barriers will be overcome and testing will become an important tool in psychiatry.
Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis.

BACKGROUND In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. METHODS We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. RESULTS We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. CONCLUSIONS These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.
Consumers’ Intentions to Adopt Blockchain-Based Personal Health Records and Data Sharing: Focus Group Study

Background Although researchers are giving increased attention to blockchain-based personal health records (PHRs) and data sharing, the majority of research focuses on technical design. Very little is known about health care consumers’ intentions to adopt the applications. Objective This study aims to explore the intentions and concerns of health care consumers regarding the adoption of blockchain-based personal health records and data sharing. Methods Three focus groups were conducted, in which 26 participants were shown a prototype of a user interface for a self-sovereign blockchain-based PHR system (ie, a system in which the individual owns, has custody of, and controls access to their personal health information) to be used for privacy and secure health data sharing. A microinterlocutor analysis of focus group transcriptions was performed to show a descriptive overview of participant responses. NVivo 12.0 was used to code the categories of the responses. Results Participants did not exhibit a substantial increase in their willingness to become owners of health data and share the data with third parties after the blockchain solution was introduced. Participants were concerned about the risks of losing private keys, the resulting difficulty in accessing care, and the irrevocability of data access on blockchain. They did, however, favor a blockchain-based PHR that incorporates a private key recovery system and offers a health wallet hosted by government or other positively perceived organizations. They were more inclined to share data via blockchain if the third party used the data for collective good and offered participants nonmonetary forms of compensation and if the access could be revoked from the third party. Conclusions Health care consumers were not strongly inclined to adopt blockchain-based PHRs and health data sharing. However, their intentions may increase when the concerns and recommendations demonstrated in this study are considered in application design.
Covid-19 and Solid Organ Transplantation: A Review Article.

The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients and end stage kidney disease patients, transplant activity during the pandemic and treatment options for COVID-19 disease.
Antimicrobial activity of amphiphilic nanomicelles loaded with curcumin against Pseudomonas aeruginosa alone and activated by blue laser light

The aim of this work was to assess the antimicrobial efficacy on Pseudomonas aeruginosa of nanomicelles loaded with curcumin (CUR) alone and activated by blue laser light in an antimicrobial photodynamic therapy (APDT) approach. First, free CUR in liquid suspension and loaded in three amphiphilic nanomicelles (CUR‐DAPMA, CUR‐SPD and CUR‐SPM) were tested both on bacteria and keratinocytes. While free CUR exerted limited efficacy showing moderate cytotoxicity, a strong inhibition of bacterial growth was obtained using all three nanosystems without toxicity on eukaryotic cells. CUR‐SPM emerged as the most effective, and was therefore employed in APDT experiments. Among the three sublethal blue laser (λ 445 nm) protocols tested, the ones characterized by a fluence of 18 and 30 J/cm2 further decreased the antimicrobial concentration to 50 nM. The combination of blue laser APDT with CUR‐SPM nanomicelles results in an effective synergistic activity that represents a promising novel therapeutic approach on resistant species.
DNA barcoding and phylogeny of Phlomis aurea (Lamiaceae) endemic to Sinai peninsula, Egypt

Taxonomy represents the baseline for biological characterization and naming for endangered plant species. Phlomis aurea has never been a subject of comprehensive biosystematics assessment. Phlomis aurea is an endangered species suffering from global changes which lead to population decline. It is important to rediscover critical biological traits related to endemic species to help set up conservation plan(s). The current study represents a comprehensive morphological and anatomical characterization of the endangered Phlomis aurea endemic to Sinai Peninsula, Egypt. Phylogenetic placement and DNA barcoding were done using two molecular markers (rbcL and psb-A/trn-H).
Foliar anatomy of Rhynchosia spp. (Leguminosae, Papilionoideae) from Roraima state, northern Brazilian Amazon

ABSTRACT Comparative studies on the structure of foliar anatomy in four species of Rhynchosia from Roraima state (northern Brazilian Amazon) were carried out to identify additional morphological characters to support the definition of the systematic boundaries among the species. Fully expanded leaves, including the petioles, were collected from the upper nodes of a plant’s stem. Anatomical characters were observed in cross-sections of the middle portion of leaflets and petiole segments. Presence and distribution of glandular trichomes, continuity of sclerenchyma around the vascular bundles in leaflet blades and the conformation of the area between the two ridges of petioles were important characters to distinguish among the species of Rhynchosia. For the first time we report a distinct multicellular gland-like structure which we found in the petioles of three species.
The Locus of Fat Over-Accumulation as Predictor of Cardiometabolic Risks among Non Obese Normotensive Adults

Studies on Metabolic Syndrome (MS) have recently been narrowed down to fat over-accumulation but there is no consistency in the obesity requirements for any of the health risk scores and definitions, thus, the utility of anthropometric measures in cardiometabolic risks prediction among non-obese requires additional research. This cross sectional study assessed the relationships and predictabilities of visceral adiposity index (VAI) and Lipid accumulation product (LAP) for cardiometabolic risks among 174 non obese adults (91 males and 83 females) 35 70 years of age that was randomly selected for this study after their consent. Anthropometric evaluation included weight, height, hip and waist circumferences. BMI, Waist-height ratio and waist-hip ratio were calculated. Serum Triglyceride and High Density Lipoprotein measured in a 12 hour fasting condition (mmol/L) using standard laboratory techniques were recorded. The VAI and LAP scores were calculated using the gender-specific equations. Systolic blood pressure and Diastolic blood pressure were measured and MABP was calculated as: DBP + 1/3 Pulse Pressure (mm/Hg). The results showed significant correlations among LAP, VAI, WHTR, WHPR and BMI (p≤0.01). Multivariate correlations and regression analysis of measures of adiposity and MS features also Original Research Article Sharaye and Eboh; JAMMR, 32(19): 27-35, 2020; Article no.JAMMR. 61453 28 showed that LAP had a greater impact on features of MS and superior to other adiposity measures in male and female (R 2 : 0.956; p≤0.01). In conclusion, this study shows that LAP is superior in predicting risks of lipid and visceral adipose over-accumulations than other measures of adiposity among non-obese adults. The use of LAP as an assessment tool for Risks of fat overaccumulations and its intervention among non-obese adults was suggested.
Personality Traits, Emotional Intelligence, Socio-contextual Factors and Spousal Violence: The Trajectory of COVID-19 Pandemic Lockdown

Introduction: Media has revealed several Spousal Violence (SV) during COVID-19 pandemic lockdown in Nigeria whereas researchers have not delved into reasons for this surge. This study investigated the psychosocial factors influencing SV during the COVID-19 pandemic lockdown. Method: A web-based cross-sectional study utilizing snowballing sampling technique was adopted and participants were recruited in Lagos, Nigeria via social media platform, Facebook and WhatsApp using google form from March 30 to April 4, 2020. For this purpose, 356 participants consisting of 141-male and 215-female responded to the Big Five Personality Inventory, Trait Emotional Intelligence and Composite Abuse Scales. Results: Personality Traits (PT) and Emotional Intelligence (EI) jointly predicted SV [R=. 267; R2=. 077; F (6, 556), t=3.281, p < . 01]. This is while, only patterns of neuroticism had independent significant prediction on SV with a positive impact [t=3.64, p < . 01, β=. 23]. Additionally, PT as a whole [t=2.54, p < . 05, β=. 22] and EI [t=2.31 p < . 05, β=-. 150] showed an independent prediction of SV (significantly) among the sampled participants with a negative impact. Also, the effect of living conditions [F=2.91, P<. 05] and job status [F=4.912, P<. 01] differ on SV among the selected participants. Conclusion: The study concluded that the surge in the SV outcomes during the COVID-19 crisis among Nigerians was caused by both psychological and socio-contextual factors. Therefore, better attention should be paid to psychological interventions and palliative measures during this pandemic or future lock-down.
Integrative Analysis of Prognostic Biomarkers for Acute Rejection in Kidney Transplant Recipients

Background. Noninvasive biomarkers may predict adverse events such as acute rejection after kidney transplantation and may be preferable to existing methods because of superior accuracy and convenience. It is uncertain how these biomarkers, often derived from a single study, perform across different cohorts of recipients. Methods. Using a cross-validation framework that evaluates the performance of biomarkers, the aim of this study was to devise an integrated gene signature set that predicts acute rejection in kidney transplant recipients. Inclusion criteria were publicly available datasets of gene signatures that reported acute rejection episodes after kidney transplantation. We tested the predictive probability for acute rejection using gene signatures within individual datasets and validated the set using other datasets. Eight eligible studies of 1454 participants, with a total of 512 acute rejections episodes were included. Results. All sets of gene signatures had good positive and negative predictive values (79%–96%) for acute rejection within their own cohorts, but the predictability reduced to <50% when tested in other independent datasets. By integrating signature sets with high specificity scores across all studies, a set of 150 genes (included CXCL6, CXCL11, OLFM4, and PSG9) which are known to be associated with immune responses, had reasonable predictive values (varied between 69% and 90%). Conclusions. A set of gene signatures for acute rejection derived from a specific cohort of kidney transplant recipients do not appear to provide adequate prediction in an independent cohort of transplant recipients. However, the integration of gene signature sets with high specificity scores may improve the prediction performance of these markers.
Application of Lip Biopsy for the Histological Diagnosis of Immunoglobulin G4-Related Disease

We describe the case of a 51-year-old woman with immunoglobulin G4-related disease (IgG4-RD) diagnosed using lip biopsy. She reported having bilateral submandibular nodules for a month. Magnetic resonance imaging showed diffuse swelling in the bilateral submandibular glands (SMGs), suggesting inflammatory changes. Laboratory data revealed an elevated level of serum IgG4. Fine needle aspiration cytology of the SMG showed a considerable number of lymphocytes with degeneration but did not demonstrate specific findings for a definitive diagnosis of IgG4-RD. Lip biopsy was performed, and a biopsy specimen from the labial salivary gland showed abundant lymphoplasmacytic infiltration with a large number of IgG4-positive cells. The patient was diagnosed with IgG4-RD based on histological and laboratory findings. Findings of further examinations revealed that the patient had autoimmune pancreatitis, confirming our diagnosis. Four months after prednisolone administration, improvement of the submandibular and pancreatic lesions was observed. One year after the initial presentation, the serum IgG4 level was normalized. In cases of IgG4-RD with salivary gland involvement, lip biopsy might be one of the options for the histological diagnosis of IgG4-RD.
Bacterial genome editing by coupling Cre-lox and CRISPR-Cas9 systems

The past decade has been a golden age for microbiology, marked by the discovery of an unprecedented increase in the number of novel bacterial species. Yet gaining biological knowledge of those organisms has not kept pace with sequencing efforts. To unlock this genetic potential there is an urgent need for generic (i.e. non-species specific) genetic toolboxes. Recently, we developed a method, termed chassis-independent recombinase-assisted genome engineering (CRAGE), enabling the integration and expression of large complex gene clusters directly into the chromosomes of diverse bacteria. Here we expand upon this technology by incorporating CRISPR-Cas9 allowing precise genome editing across multiple bacterial species. To do that we have developed a landing pad that carries one wild-type and two mutant lox sites to allow integration of foreign DNA at two locations through Cre-lox recombinase-mediated cassette exchange (RMCE). The first RMCE event is to integrate the Cas9 and the DNA repair protein genes RecET, and the second RMCE event enables the integration of customized sgRNA and a repair template. Following this workflow, we achieved precise genome editing in four different gammaproteobacterial species. We also show that the inserted landing pad and the entire editing machinery can be removed scarlessly after editing. We report here the construction of a single landing pad transposon and demonstrate its functionality across multiple species. The modular design of the landing pad and accessory vectors allows design and assembly of genome editing platforms for other organisms in a similar way. We believe this approach will greatly expand the list of bacteria amenable to genetic manipulation and provides the means to advance our understanding of the microbial world.
Trisulfide bond–mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity

Trisulfide bond enhances the stability and GSH sensitivity of doxorubicin dimeric prodrug nanoassemblies. Rational design of nanoparticulate drug delivery systems (nano-DDS) for efficient cancer therapy is still a challenge, restricted by poor drug loading, poor stability, and poor tumor selectivity. Here, we report that simple insertion of a trisulfide bond can turn doxorubicin homodimeric prodrugs into self-assembled nanoparticles with three benefits: high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity. Compared with disulfide and thioether bonds, the trisulfide bond effectively promotes the self-assembly ability of doxorubicin homodimeric prodrugs, thereby improving the colloidal stability and in vivo fate of prodrug nanoassemblies. The trisulfide bond also shows higher glutathione sensitivity compared to the conventional disulfide bond, and this sensitivity enables efficient tumor-specific drug release. Therefore, trisulfide bond–bridged prodrug nanoassemblies exhibit high selective cytotoxicity on tumor cells compared with normal cells, notably reducing the systemic toxicity of doxorubicin. Our findings provide new insights into the design of advanced redox-sensitive nano-DDS for cancer therapy.
In vitro study of postbiotics from Lactobacillus plantarum RG14 on rumen fermentation and microbial population

ABSTRACT An in vitro study was carried out to identify the effects of different inclusion levels of postbiotics from Lactobacillus plantarum RG14 on rumen fermentation profiles, gas production kinetics, and microbial population in rumen fluid collected from goats. Postbiotics were added at different levels (0, 0.3, 0.6, 0.9, and 1.2%) and incubated for 72 h with 200 mg dry matter (DM) of a substrate containing 60% Guinea grass and 40% commercial concentrate. The experiment was conducted in triplicate on different [. ]