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Purpose: The local management approach for node-positive breast cancer has undergone substantial evolution. Consequently, there exists a pressing need to enhance our treatment strategies by placing greater emphasis on planning and dosimetric factors, given the availability of more conformal techniques and delineation criteria, achieving optimal goals of radiotherapy treatment. The primary aim of this article is to discuss how the extent of regional nodal coverage influences the choice between IMRT and 3D radiation therapy for patients. Patients and Methods: A total of 15 patients diagnosed with left breast cancer with disease involved lymph nodes were included in this study. Delivering the recommended dose required the use of a linear accelerator (LINAC) with photon beams energy of 6 mega voltage (6MV). Each patient had full breast radiation using two planning procedures: intensity-modulated radiotherapy (IMRT) and three-dimensional radiotherapy (3D conformal). Following the guidelines set forth by the Radiation Therapy Oncology Group (RTOG), the planned treatment coverage was carefully designed to fall between 95% and 107% of the recommended dose. Additionally, Dose Volume Histograms (DVHs) were generated the dose distribution within these anatomical contours. Results and Conclusion: The DVH parameters were subjected to a comparative analysis, focusing on the doses absorbed by both Organs at Risk (OARs) and the Planning Target Volume (PTV). The findings suggest that low doses in IMRT plan might raise the risk of adverse oncological outcomes or potentially result in an increased incidence of subsequent malignancies. Consequently, the adoption of inverse IMRT remains limited, and the decision to opt for this therapy should be reserved for situations where it is genuinely necessary to uphold a satisfactory quality of life. Additionally, this approach helps in reducing the likelihood of developing thyroid problems and mitigates the risk of injuries to the supraclavicular area and the proximal head of the humerus bone.

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Numerous traditional practices are both beneficial and harmful. Traditional harmful practices, such as female genital mutilation and traditional cervical cauterization, are carried out for a number of reasons but can have negative health and social effects. In addition to deeply held beliefs, a lack of knowledge and awareness of the consequences of these practices contributes to the persistence of these issues. The objective of this study is to examine whether traditional cervical cauterizations were associated with preterm births in Somalia. This prospective cohort study was conducted at our hospital over a one-year period. Seven hundred and two patients were included in this study; these patients were divided into two groups, cauterized and non-cauterized groups, and the two groups were compared on pregnancy outcomes. We examined whether traditional cervical cauterizations were associated with adverse pregnancy outcomes, including preterm births. According to the findings of this study, traditional cervical cauterization was prevalent among patients visiting MSTREH (n = 328, 46.7%). Infections of the uterine cervix and infertility were the two main indications for cauterization, 44.8%, and 34.8%, respectively.Being older, uneducated, and poverty were significantly associated with traditional cauterization (P < 0.001). There was a significant correlation between prior traditional cervical cauterization and the risk of preterm births. Women with prior cauterization were two and half times more likely to deliver a preterm fetus (OR: 2.64, 95% CI 2.15-3.33) compared to non-cauterized mothers. Our findings show that women who have previously undergone traditional cervical cauterization have a significantly higher risk of preterm birth and negative pregnancy outcomes than non-cauterized women. Health professionals, particularly those who are close to the community, are crucial in developing and putting into practice plans to end harmful traditions in Somalia.

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The Editorial Board has retracted this article. After publication, concerns were raised about this study's reported data. We reached out to the authors to request their raw data, but they could not provide. Therefore, the Editorial Board no longer has confidence in the results presented.

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Background: In developing countries, institutional delivery is a key proven intervention that reduces maternal mortality and can reduce maternal deaths by approximately 16%-33%. In Somalia, only 32% of births are delivered in a health facility with the assistance of a skilled healthcare provider. We aimed to investigate the factors hindering women from giving birth at healthcare facilities in major towns in Somalia, where most of the health facilities in the country are concentrated. Methods: A community-based health survey was carried out in 11 major towns in Somalia between October and December 2021. A structured and pretested questionnaire was used to collect data from 430 women who gave birth in the last five years. Women were recruited through convenient sampling. Descriptive statistics were used to summarize the data, and binary and multivariable logistic regression analysis was performed. Adjusted odds ratios (AOR) with 95% CI were estimated to assess the associations. Results: The overall prevalence of institutional delivery was 57%. Approximately 38% of women living in Mogadishu and 53% living in another ten towns give birth at home. Women who had poor knowledge of the importance of health facility delivery had nearly four times higher odds of delivering at home (AOR 3.64 CI: 1.49-8.93). Similarly, those who did not receive antenatal care (AOR 2.5, CI: 1.02-6.39) and those who did not receive a consultation on the place of delivery (AOR 2.15, CI: 1.17-3.94) were more likely to give birth at home. The reasons for home delivery included financial reasons, the long distance to the health facility, and the fact that it was easier to give birth at home. Conclusion: The study found that home delivery is high in major towns in Somalia and is associated with a lack of understanding of the importance of health facility delivery, not using ANC, and not receiving consultancy about where to give birth. Primary health care should strengthen information, education, and communication activities. Since the health care system in Somalia is overwhelmingly private, the government may consider access to free and within-reach ANC and health facility delivery for women and girls from families who cannot pay the ANC and childbirth delivery cost.

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The use of nano additives to improve the cold properties of biodiesel is encouraged by its drawbacks and incompatibility in cold climate. Waste cooking oil (WCO) was transesterified to create biodiesel. A 20% by volume was used for combination of diesel and methyl ester. Current study aims to evaluate diesel engine emissions and performance. TiO2, alumina, and hybrid TiO2 + Al2O3 nanoparticles are added to WCO biodiesel mixture at 25 mg/liter. When B20 combined with nano materials such as TiO2, Al2O3, and hybrid nano, the highest declines in brake specific fuel consumption were 4, 6, and 11%, respectively. As compared to biodiesel blend, the largest gains in thermal efficiency were 4.5, 6.5, and 12.5%, respectively, at maximum engine output power. Introduction of TiO2, Al2O3, and hybrid nano particles to B20 at 100% load resulted in the highest decreases in HC concentrations up to 7, 13, and 20%, and the biggest reductions in CO emissions, up to 6, 12, and 16%. Largest increases in NOx concentrations at full load were about 7, 15, and 23% for B20 + 25TiO2, B20 + 25 Al2O3, and B20 + 25TiO2 + 25 Al2O3, respectively. Up to 8, 15, and 21% less smoke was released, correspondingly, which were the largest reductions. Recommended dosage of 25 ppm alumina and 25 ppm TiO2 achieved noticeable improvements in diesel engine performance, combustion and emissions about B20.

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Mitochondrial dysfunction is linked to various systemic and localized diseases, including oral diseases like periodontitis, oral cancer, and temporomandibular joint disorders. This paper explores the intricate mechanisms underlying mitochondrial dysfunction in oral pathologies, encompassing oxidative stress, inflammation, and impaired energy metabolism. Furthermore, it elucidates the bidirectional relationship between mitochondrial dysfunction and oral diseases, wherein the compromised mitochondrial function exacerbates disease progression, while oral pathologies, in turn, exacerbate mitochondrial dysfunction. Understanding these intricate interactions offers insights into novel therapeutic strategies targeting mitochondrial function for managing oral diseases. This paper pertains to the mechanisms underlying mitochondrial dysfunction, its implications in various oral pathological and inflammatory conditions, and emerging versatile treatment approaches. It reviews current therapeutic strategies to mitigate mitochondrial dysfunction, including antioxidants, mitochondrial-targeted agents, and metabolic modulators.

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Objective: We described the technique and outcomes of robot-assisted repair of uretero-enteric strictures (UES) following robot-assisted radical cystectomy (RARC) and urinary diversion. Methods: Retrospective review of our RARC database from November 2005 to August 2023 at Roswell Park Comprehensive Cancer center was performed. Patients who developed UES and ultimately underwent robot-assisted uretero-enteric reimplantation (RUER) were identified. Kaplan-Meier method was used to compute the cumulative incidence recurrence rate of UES after RUER. A multivariable regression model was used to identify variables associated with UES recurrence. Results: A total of 123 (15%) out of 808 RARC patients developed UES, of whom 52 underwent reimplantation (45 patients underwent RUER [n=55 cases] and seven patients underwent open uretero-enteric reimplantation). The median time from RARC to UES was 4.4 (interquartile range 3.0-7.0) months, and the median time between UES and RUER was 5.2 (interquartile range 3.2-8.9) months. The 3-year recurrence rate after RUER is about 29%. On multivariable analysis, longer hospital stay (hazard ratio 1.37, 95% confidence interval 1.16-1.61, p<0.01) was associated with recurrent UES after RUER. Conclusion: RUER for UES after RARC is feasible with durable outcomes although a notable subset of patients experienced postoperative complications and UES recurrence.

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Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.

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BACKGROUND: Placenta accreta spectrum disorders are associated with a high risk of maternal morbidity, particularly when surgery is performed under emergency conditions. This study aimed to investigate the incidence of emergency cesarean delivery in patients with a high probability of placenta accreta spectrum disorders on prenatal imaging and to compare the maternal and neonatal outcomes between patients requiring emergency cesarean delivery and those not requiring emergency cesarean delivery. DATA SOURCES: MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases were searched. STUDY ELIGIBILITY CRITERIA: This study included case-control studies reporting the outcomes of pregnancies with a high probability of placenta accreta spectrum on prenatal imaging confirmed at birth delivered via unplanned emergency cesarean delivery vs those delivered via planned elective cesarean delivery for maternal or fetal indications. The outcomes observed were the occurrence of emergency cesarean delivery; incidence of placenta accreta and placenta increta/placenta percreta; preterm birth at <34 weeks of gestation; and indications for emergency delivery. This study analyzed and compared the outcomes between patients who underwent emergency cesarean delivery and those who underwent elective cesarean delivery, including estimated blood loss; number of packed red blood cell units transfused and blood products transfused; transfusion of more than 4 units of packed red blood cell; ureteral, bladder, or bowel injury; disseminated intravascular coagulation; relaparotomy after the primary surgery; maternal infection or fever; wound infection; vesicouterine or vesicovaginal fistula; admission to the neonatal intensive care unit; maternal death; composite neonatal morbidity; fetal or neonatal loss; Apgar score of <7 at 5 minutes; and neonatal birthweight. METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for case-control and cohort studies. Random-effect meta-analyses of proportions, risks, and mean differences were used to combine the data. RESULTS: A total of 11 studies with 1290 pregnancies complicated by placenta accreta spectrum were included in the systematic review. Emergency cesarean delivery was reported in 36.2% of pregnancies (95% confidence interval, 28.1-44.9) with placenta accreta spectrum at birth, of which 80.3% of cases (95% confidence interval, 36.5-100.0) occurred before 34 weeks of gestation. The main indication for emergency cesarean delivery was antepartum bleeding, which complicated 61.8% of the cases (95% confidence interval, 32.1-87.4). Patients who underwent emergent cesarean delivery had higher estimated blood loss during surgery (pooled mean difference, 595 mL; 95% confidence interval, 116.10-1073.90; P<.001), higher number of packed red blood cells transfused (pooled mean difference, 2.3 units; 95% confidence interval, 0.99-3.60; P<.001), and higher number of blood products transfused (pooled mean difference, 3.0; 95% confidence interval, 1.10-4.90; P=.002) than patients who underwent scheduled cesarean delivery. Patients who underwent emergency cesarean delivery had a higher risk of requiring transfusion of more than 4 units of packed red blood cell (odds ratio, 3.8; 95% confidence interval, 1.7-4.9; P=.002), bladder injury (odds ratio, 2.1; 95% confidence interval, 1.1-4.0; P=.003), disseminated intravascular coagulation (odds ratio, 6.1; 95% confidence interval, 3.1-13.1; P<.001), and admission to the intensive care unit (odds ratio, 2.1; 95% confidence interval, 1.4-3.3; P<.001). Newborns delivered via emergency cesarean delivery had a higher risk of adverse composite neonatal outcomes (odds ratio, 2.6; 95% confidence interval, 1.4-4.7; P=.019), admission to the neonatal intensive care unit (odds ratio, 2.5; 95% confidence interval, 1.1-5.6; P=.029), Apgar score of <7 at 5 minutes (odds ratio, 2.7; 95% confidence interval, 1.5-4.9; P=.002), and fetal or neonatal loss (odds ratio, 8.2; 95% confidence interval, 2.5-27.4; P<.001). CONCLUSION: Emergency cesarean delivery complicates approximately 35% of pregnancies affected by placenta accreta spectrum disorders and is associated with a higher risk of adverse maternal and neonatal outcomes. Large prospective studies are needed to evaluate the clinical and imaging signs that can identify patients with a high probability of placenta accreta spectrum at birth, patients at risk of requiring emergency cesarean delivery or peripartum hysterectomy, and patients at high risk of experiencing intrapartum hemorrhage.

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OBJECTIVE: To evaluate the utility of low-cost simulation models to teach surgical techniques for placenta accreta spectrum (PAS), included in a multimodal education workshop for PAS. METHODS: This was an observational, survey-based study. Participants were surveyed before and after the use of low-fidelity mannequins to simulate two surgical techniques for PAS (one-step conservative surgery [OSCS] and modified subtotal hysterectomy [MSTH]), within a multimodal educational workshop. The workshops included pre-course preparation, didactics, simulated practice of the techniques using low-cost models, and viewing live surgery. RESULTS: Six OSCS/MSTH training workshops occurred across six countries and a total of 270 participants were surveyed. The responses of 127 certified obstetricians and gynecologists (OB-GYNs) were analyzed. Participants expressed favorable impressions of all components of the simulated session. Perceived anatomical simulator fidelity, scenario realism, educational component effectiveness, and self-assessed performance improvement received ratings of 4-5 (positive end of the Likert scale) from over 90% of respondents. When asked about simulation's role in technique comprehension, comfort level in technique performance, and likelihood of recommending this workshop to others, more than 75% of participants rated these aspects with a score of 4-5 (positively) on the five-point scale. CONCLUSION: Low-cost simulation, within a multimodal education strategy, is a well-accepted intervention for teaching surgical techniques for PAS.

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Introduction and Hypothesis: Robot-assisted radical nephroureterectomy (RANU) has emerged as a valid alternative to open or laparoscopic nephroureterectomy in recent years. However, different types of robotic platforms can limit surgical maneuvers in various ways. This study aimed to describe the surgical procedure and demonstrate RANU's technical feasibility and safety using the Hugo robot-assisted surgery (RAS) system. Materials and Methods: Using the Hugo RAS system, we reported data from the first five consecutive patients who underwent RANU at Tottori University Hospital. We adjusted the docking angles of the four independent arm carts in each case and performed a complete RANU via a transperitoneal approach. We collected patients' sociodemographic and perioperative data, including complications, and compared them retrospectively with data obtained using the da Vinci surgical system. Results: Arms positions were modified after the first patient to be placed all at the back of the patient. Median overall operative time was 283 minutes (203-377) and the median time using the robotic system was 187 minutes (121-277). The median estimated blood loss was 20 mL (5-155). None of the patients required a blood transfusion and none suffered postoperative complications of Clavien-Dindo grade ≥3. These outcomes were similar to those obtained with the da Vinci Xi system. Conclusion: This series represents the first report of RANU executed using the novel Hugo RAS system. Our proposed arm-setup will assist other surgeons and help ensure safe implementation of RANU on the Hugo platform.

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Background: ß-thalassemia major is microcytic hypochromic anemia disorder inherited from parents, resulting from a mutation in the ß-globin locus. As a result, a quantitative defective hemoglobin synthesis and relative excess in α-globin is occurred. As such, frequent blood transfusion is required, that leads to iron overload. Iron overload results in several pathological complications, including cell death, tissue injury, organ dysfunction, and liver fibrosis. The present study examined the effectiveness of nigella Sativa and manuka honey combination or manuka honey alone to the conventional therapy (Deferasirox + blood transfusion) used for preventing and managing iron overload in pediatric ß-thalassemia major patients. Methods: One hundred sixty-five patients participated in this randomized, double-blind, standard therapy-controlled, parallel-design multisite trial. The patients were randomly allocated into three groups, receiving either 500 mg nigella sativa oil combined with manuka honey lozenge (344 mg) daily or manuka honey alone plus the conventional therapy for ten treatment months. Ferritin level, serum iron, transferrin saturation, total iron binding capacity, alanine transaminase, and aspartate transaminase were determined at baseline and month 10. Results: Eventually, serum ferritin and iron were decreased significantly in the nigella sativa + manuka honey group as compared with the control group. Other clinical parameters were significantly impacted. The level of alanine transaminase and aspartate transaminase were significantly decreased in the nigella sativa plus manuka honey group compared with the control group. Conclusion: Results showed that nigella sativa plus manuka honey was more effective than manuka alone or the conventional treatment alone in managing iron overload of ß-thalassemia major patients.

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BACKGROUND: Despite the success of sleeve gastrectomy (SG) in of weight loss and treatment of the medical problems associated with obesity, some concerns have arisen about the need for revisional surgeries after SG in some patients. This study aimed to present an updated and comprehensive comparison among the presently available revisional surgeries employed explicitly in cases of inadequate outcomes after SG, which is the most frequently performed bariatric surgery in contemporary practice. METHODS: This network meta-analysis included studies that compared the outcomes of different revisional bariatric procedures after an inadequate outcome of SG. RESULTS: Searching across the electronic databases yielded 31 eligible articles. Re-SG was associated with the highest rate of significant complications. Patients treated with single anastomosis duodenal-ileal bypass (SADI) had a significantly higher percentage of total weight loss (%TWL) than those treated with one anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB). The percentage of excess weight loss (%EWL) at the end of the follow-up period was significantly higher in patients in the SADI group compared to those in the RYGB group and the OAGB, and re-SG exhibited the least values compared to SADI, biliopancreatic diversion with duodenal switch (BPD/DS), and OAGB. Significantly lower rates of reflux worsening/de novo development were observed in the SADI group compared to the OAGB group and the re-SG group, which showed significantly higher rates than SADI and RYGB. CONCLUSION: Our comprehensive network meta-analysis highlights SADI as a promising revisional option post-SG, demonstrating superior weight loss outcomes, lower significant complication rates, and a favorable impact on reflux compared to other procedures. While acknowledging the limitations of our study, these findings support the potential efficacy of SADI in addressing the challenges of inadequate weight loss after sleeve gastrectomy.

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Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity of pure phenolic compounds has not been reported yet. The chromatographic of a methanolic extract yielded twenty-two compounds, viz.: naringenin 4'-O-glucoside (1), 3',4',7-trihydroxyflavanone (butin) (2), liquiritin (3), liquiritin apioside (4), abyssinone (5), glabrol (6), isoliquiritin (7), neoisoliquiritin (8), isoliquiritin apioside (9), licuraside (10). 3'[O], 4'-(2,2-dimethylpyrano)-3,7-dihydroxyflavanone (11), glabrocoumarin (12), glabrene (13), isomedicarpin (14), 7-hydroxy-4'-methoxyflavone (formononetin) (15), ononin (16), glycyroside (17), (3S)-7,4'-dihydroxy-2'-methoxyisoflavan (18), glabridin (19), neoliquiritin (20), 3,11-dioxooleana-1,12-dien-29-oic acid (21), and 3-oxo-18ß-glycyrrhetinic acid (22). The results of the neuroprotection evaluation showed that G. glabra total extract (TE) and compounds 1, 7, 11, 16, and 20 protected SH-SY5Y cells by inhibiting the depletion of ATP and elevated caspase 3/7 activities induced by MPP+. Indeed, this study reports for the first time the structure and activity of compound 11 and the neuroprotective activity of some phenolic constituents from G. glabra.

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More than 800,000 people worldwide are diagnosed with HCC (hepatocellular carcinoma) each year, with approximately 700,000 deaths alone occurring in that same year. Treatment of HCC presents complex therapeutic challenges, particularly in intermediate and advanced stages. LRTs such as transarterial chemoembolization (TACE) and ablations have been the mainstay treatment for early to intermediate-stage HCC, and systemic therapies are used to treat intermediate-late-stage HCC. However, novel literature describing combining LRT with systemic therapies has shown promising results. This review explores recent advances in both liver-directed techniques for hepatocellular carcinoma, including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies in conjunction as well as with systemic therapies, with a focus on combination therapies, patient selection, procedural technique, periprocedural management, and outcomes. Our findings suggest that LRT combined with systemic therapies is a viable strategy for improving progression-free survival and time to progression for patients with intermediate-to-late-stage HCC. However, further investigation is required to refine treatment protocols and define patient cohorts that would benefit the most.

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BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

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Tephrosia vogelii is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CH2Cl2/MeOH (1:1) roots extract of T. vogelii afforded seven compounds namely; ß-sitosterol (1a), stigmasterol (1b), 6a, 12a-dehydro-deguelin (2), tephrosin (3), maackiain (4), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6). GC-MS analysis of essential oils from the root of T. vogelii displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were the major constituents. CH2Cl2/MeOH (1:1) extract, MeOH extract, maackiain (4) and obovatin (5) showed moderate inhibitory activity against Pseudomonas aeruginosa with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 µg/mL). 6a, 12a-dihydro-deguelin (2), and 6-oxo, 6a, 12a-dehydro-deguelin (6) displayed significant activity against S. epidermis with MIC values of 0.66 mg/mL. Tephrosin (3) and maackiain (4) also showed moderate antibacterial activity against Staphylococcus aureus and Proteus mirabilis with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 µg/mL). The radical scavenging activity results indicated that tephrosin (3), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6) showed potent DPPH scavenging activity with IC50 values of 10.97, 10.43 and 10.73 µg/mL, respectively, compared to ascorbic acid (IC50 of 5.83 µg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin (2) displayed the best binding energy of -8.1 kcal/mol towards pyruvate kinase of S. aureus (PDB ID: 3T07) and -7.9 kcal/mol towards P. mirabilis urease (PDB ID: 1E9Y) and DNA gyrase B of Escherichia coli (PDB: 4F86) receptors compared to ciprofloxacin (-7.2 to -8.0 kcal/mol). Maackiain (4) and obovatin (5) displayed the minimum binding energy of -7.9 and -8.2 kcal/mol towards the LasR protein of P. aeruginosa (PDB: ID 2UV) and S. epidermidis FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds (2-6) obeyed Lipinski's rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The in vitro assessment results supported by the in silico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of T. vogelii.

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BACKGROUND: The current scores used to help diagnose acute appendicitis have a "gray" zone in which the diagnosis is usually inconclusive. Furthermore, the universal use of CT scanning is limited because of the radiation hazards and/or limited resources. Hence, it is imperative to have an accurate diagnostic tool to avoid unnecessary, negative appendectomies. METHODS: This was an international, multicenter, retrospective cohort study. The diagnostic accuracy of the artificial intelligence platform was assessed by sensitivity, specificity, negative predictive value, the area under the receiver curve, precision curve, F1 score, and Matthews correlation coefficient. Moreover, calibration curve, decision curve analysis, and clinical impact curve analysis were used to assess the clinical utility of the artificial intelligence platform. The accuracy of the artificial intelligence platform was also compared to that of CT scanning. RESULTS: Two data sets were used to assess the artificial intelligence platform: a multicenter real data set (n = 2,579) and a well-qualified synthetic data set (n = 9736). The platform showed a sensitivity of 92.2%, specificity of 97.2%, and negative predictive value of 98.7%. The artificial intelligence had good area under the receiver curve, precision, F1 score, and Matthews correlation coefficient (0.97, 86.7, 0.89, 0.88, respectively). Compared to CT scanning, the artificial intelligence platform had a better area under the receiver curve (0.92 vs 0.76), specificity (90.9 vs 53.3), precision (99.8 vs 98.9), and Matthews correlation coefficient (0.77 vs 0.72), comparable sensitivity (99.2 vs 100), and lower negative predictive value (67.6 vs 99.5). Decision curve analysis and clinical impact curve analysis intuitively revealed that the platform had a substantial net benefit within a realistic probability range from 6% to 96%. CONCLUSION: The current artificial intelligence platform had excellent sensitivity, specificity, and accuracy exceeding 90% and may help clinicians in decision making on patients with suspected acute appendicitis, particularly when access to CT scanning is limited.

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BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

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