BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis.

For tumors to progress efficiently, cancer cells must overcome barriers of oxidative stress. Although dietary antioxidant supplementation or activation of endogenous antioxidants by NRF2 reduces oxidative stress and promotes early lung tumor progression, little is known about its effect on lung cancer metastasis. Here, we show that long-term supplementation with the antioxidants N-acetylcysteine and vitamin E promotes KRAS-driven lung cancer metastasis. The antioxidants stimulate metastasis by reducing levels of free heme and stabilizing the transcription factor BACH1. BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. Targeting BACH1 normalized glycolysis and prevented antioxidant-induced metastasis, while increasing endogenous BACH1 expression stimulated glycolysis and promoted metastasis, also in the absence of antioxidants. We conclude that BACH1 stimulates glycolysis-dependent lung cancer metastasis and that BACH1 is activated under conditions of reduced oxidative stress.

Heterogeneous integration of spin-photon interfaces with a CMOS platform.

Colour centres in diamond have emerged as a leading solid-state platform for advancing quantum technologies, satisfying the DiVincenzo criteria1 and recently achieving quantum advantage in secret key distribution2. Blueprint studies3-5 indicate that general-purpose quantum computing using local quantum communication networks will require millions of physical qubits to encode thousands of logical qubits, presenting an open scalability challenge. Here we introduce a modular quantum system-on-chip (QSoC) architecture that integrates thousands of individually addressable tin-vacancy spin qubits in two-dimensional arrays of quantum microchiplets into an application-specific integrated circuit designed for cryogenic control. We demonstrate crucial fabrication steps and architectural subcomponents, including QSoC transfer by means of a 'lock-and-release' method for large-scale heterogeneous integration, high-throughput spin-qubit calibration and spectral tuning, and efficient spin state preparation and measurement. This QSoC architecture supports full connectivity for quantum memory arrays by spectral tuning across spin-photon frequency channels. Design studies building on these measurements indicate further scaling potential by means of increased qubit density, larger QSoC active regions and optical networking across QSoC modules.

Structural evidence for intermediates during O2 formation in photosystem II.

In natural photosynthesis, the light-driven splitting of water into electrons, protons and molecular oxygen forms the first step of the solar-to-chemical energy conversion process. The reaction takes place in photosystem II, where the Mn4CaO5 cluster first stores four oxidizing equivalents, the S0 to S4 intermediate states in the Kok cycle, sequentially generated by photochemical charge separations in the reaction center and then catalyzes the O-O bond formation chemistry1-3. Here, we report room temperature snapshots by serial femtosecond X-ray crystallography to provide structural insights into the final reaction step of Kok's photosynthetic water oxidation cycle, the S3→[S4]→S0 transition where O2 is formed and Kok's water oxidation clock is reset. Our data reveal a complex sequence of events, which occur over micro- to milliseconds, comprising changes at the Mn4CaO5 cluster, its ligands and water pathways as well as controlled proton release through the hydrogen-bonding network of the Cl1 channel. Importantly, the extra O atom Ox, which was introduced as a bridging ligand between Ca and Mn1 during the S2→S3 transition4-6, disappears or relocates in parallel with Yz reduction starting at approximately 700 µs after the third flash. The onset of O2 evolution, as indicated by the shortening of the Mn1-Mn4 distance, occurs at around 1,200 µs, signifying the presence of a reduced intermediate, possibly a bound peroxide.

DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer.

TAp63α, a homolog of the p53 tumor suppressor, is a quality control factor in the female germline. Remarkably, already undamaged oocytes express high levels of the protein, suggesting that TAp63α's activity is under tight control of an inhibitory mechanism. Biochemical studies have proposed that inhibition requires the C-terminal transactivation inhibitory domain. However, the structural mechanism of TAp63α inhibition remains unknown. Here, we show that TAp63α is kept in an inactive dimeric state. We reveal that relief of inhibition leads to tetramer formation with ∼20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63α is not reversible by dephosphorylation. Furthermore, we show that a helix in the oligomerization domain of p63 is crucial for tetramer stabilization and competes with the transactivation domain for the same binding site. Our results demonstrate how TAp63α is inhibited by complex domain-domain interactions that provide the basis for regulating quality control in oocytes.

Genetic potential and inheritance pattern of agronomic traits in faba bean under free and infested Orobanche soil conditions.

BACKGROUND: Orobanche is an obligate parasite on faba bean in the Mediterranean region, causes considerable yield losses. Breeding tolerant faba bean genotypes to Orobanche is pivotal to sustain production and ensuring global food security, particularly considering the challenges posed by population growth. In the present study, seven faba bean lines and four testers were used in a line×tester mating design during 2020-2021 and 2021-2022 growing seasons. The eleven parents and their 28 F1 crosses were evaluated under Orobanche free and naturally infested soils. RESULTS: The results demonstrated considerable variations among the evaluated genotypes, wide diversity among the parental materials, and heterotic effects for all studied agronomic traits under Orobanche-free and infested soils. Orbanche infestation displayed a significant adverse impact on all the studied agronomic traits. The genotypes Line1, Line2, Line3, and Line5 displayed superior performance under Orobanche-infested conditions and recorded the highest values of all studied agronomic traits. Additionally, Line1, Line2, Line3, Line5, and Line7 exhibited desirable significant GCA for most evaluated traits under the two infestation conditions. The obtained crosses displayed significant negative or positive heterosis for studied agronomic characters such as plant height, number of branches per plant, number of pods per plant, number of seeds per plant, and seed weight per plant were observed. Furthermore, specific cross combinations such as Line2×Sakha3, Line3×Nubaria5, Line7 × Nubaria5, Line6×Nubaria1, Line5×Sakha3, Line1×Sakha3, and Line1 × Nubaria5 exhibited superior performance in seed yield and contributing traits under Orobanche-infested conditions. Moreover, these specific crosses showed superior efficacy in reducing dry weight of Orobanche spikes. The results obtained from GGE biplot analysis closely aligned with those from the line×tester procedure, affirming the significance of GGE biplot as a valuable statistical tool for assessing genotype combining ability in line× tester data. Both additive and non-additive gene actions were reported to be predominantly involved in the inheritance of the studied agronomic traits in faba bean. CONCLUSIONS: The detected genetic diversity within the evaluated faba bean genotypes and their developed crosses exhibits substantial potential for improving faba bean productivity under Orobanche-infested conditions. The parental genotypes, Line1, Line2, Line3, Line5, and Line7, were identified as effective and promising combiners. Moreover, the developed crosses Line2×Sakha3, Line3×Nubaria5, Line7×Nubaria5, Line6×Nubaria1, Line5×Sakha3, Line1×Sakha3, and Line1×Nubaria5 could be considered valuable candidates for developing high-yielding and tolerant faba bean genotypes to Orobanche.

Ameliorative impacts of gamma-aminobutyric acid (GABA) on seedling growth, physiological biomarkers, and gene expression in eight wheat (Triticum aestivum L.) cultivars under salt stress.

Plants spontaneously accumulate γ-aminobutyric acid (GABA), a nonprotein amino acid, in response to various stressors. Nevertheless, there is limited knowledge regarding the precise molecular mechanisms that plants employ to cope with salt stress. The objective of this study was to investigate the impact of GABA on the salt tolerance of eight distinct varieties of bread wheat (Triticum aestivum L.) by examining plant growth rates and physiological and molecular response characteristics. The application of salt stress had a detrimental impact on plant growth markers. Nevertheless, the impact was mitigated by the administration of GABA in comparison to the control treatment. When the cultivars Gemmiza 7, Gemmiza 9, and Gemmiza 12 were exposed to GABA at two distinct salt concentrations, there was a substantial increase in both the leaf chlorophyll content and photosynthetic rate. Both the control wheat cultivars and the plants exposed to salt treatment and GABA treatment showed alterations in stress-related biomarkers and antioxidants. This finding demonstrated that GABA plays a pivotal role in mitigating the impact of salt treatments on wheat cultivars. Among the eight examined kinds of wheat, CV. Gemmiza 7 and CV. Gemmiza 11 exhibited the most significant alterations in the expression of their TaSOS1 genes. CV. Misr 2, CV. Sakha 94, and CV. Sakha 95 exhibited the highest degree of variability in the expression of the NHX1, DHN3, and GR genes, respectively. The application of GABA to wheat plants enhances their ability to cope with salt stress by reducing the presence of reactive oxygen species (ROS) and other stress indicators, regulating stomatal aperture, enhancing photosynthesis, activating antioxidant enzymes, and upregulating genes involved in salt stress tolerance.

Impact of Anti-PEG IgM Induced via the Topical Application of a Cosmetic Product Containing PEG Derivatives on the Antitumor Effects of PEGylated Liposomal Antitumor Drug Formulations in Mice.

Poly(ethylene glycol) (PEG) is used in many common products, such as cosmetics. PEG, however, is also used to covalently conjugate drug molecules, proteins, or nanocarriers, which is termed PEGylation, to serve as a shield against the natural immune system of the human body. Repeated administration of some PEGylated products, however, is known to induce anti-PEG antibodies. In addition, preexisting anti-PEG antibodies are now being detected in healthy individuals who have never received PEGylated therapeutics. Both treatment-induced and preexisting anti-PEG antibodies alter the pharmacokinetic properties, which can result in a subsequent reduction in the therapeutic efficacy of administered PEGylated therapeutics through the so-called accelerated blood clearance (ABC) phenomenon. Moreover, these anti-PEG antibodies are widely reported to be related to severe hypersensitivity reactions following the administration of PEGylated therapeutics, including COVID-19 vaccines. We recently reported that the topical application of a cosmetic product containing PEG derivatives induced anti-PEG immunoglobulin M (IgM) in a mouse model. Our finding indicates that the PEG derivatives in cosmetic products could be a major cause of the preexistence of anti-PEG antibodies in healthy individuals. In this study, therefore, the pharmacokinetics and therapeutic effects of Doxil (doxorubicin hydrochloride-loaded PEGylated liposomes) and oxaliplatin-loaded PEGylated liposomes (Liposomal l-OHP) were studied in mice. The anti-PEG IgM antibodies induced by the topical application of cosmetic products obviously accelerated the blood clearance of both PEGylated liposomal formulations. Moreover, in C26 tumor-bearing mice, the tumor growth suppressive effects of both Doxil and Liposomal l-OHP were significantly attenuated in the presence of anti-PEG IgM antibodies induced by the topical application of cosmetic products. These results confirm that the topical application of a cosmetic product containing PEG derivatives could produce preexisting anti-PEG antibodies that then affect the therapeutic efficacy of subsequent doses of PEGylated therapeutics.

3-Chloropropylbis(catecholato)silicate as a Bifunctional Reagent for the One-Pot Synthesis of Tetrahydroquinolines from o-Bromosulfonamides.

Bis(catecholato)silicate salts are easily accessible reagents that can be used to install alkyl fragments through photoredox-enabled cross-coupling. These reagents can incorporate various functional groups including pendant alkyl halides. A halogenated organosilicate reagent was leveraged to develop a one-pot synthesis of tetrahydroquinolines from o-bromosulfonamides, where the bifunctional reagent participates in a nickel/photoredox cross-coupling followed by intramolecular nucleophilic substitution. The functional group tolerance of this cross-coupling strategy allowed for the preparation of a series of substituted tetrahydroquinolines.

Imaging after Pancreatic Surgery: Expected Findings and Postoperative Complications.

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. DATA SOURCES: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. STUDY SELECTION AND DATA EXTRACTION: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. DATA SYNTHESIS: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. CONCLUSIONS: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

Structures of the intermediates of Kok's photosynthetic water oxidation clock.

Inspired by the period-four oscillation in flash-induced oxygen evolution of photosystem II discovered by Joliot in 1969, Kok performed additional experiments and proposed a five-state kinetic model for photosynthetic oxygen evolution, known as Kok's S-state clock or cycle1,2. The model comprises four (meta)stable intermediates (S0, S1, S2 and S3) and one transient S4 state, which precedes dioxygen formation occurring in a concerted reaction from two water-derived oxygens bound at an oxo-bridged tetra manganese calcium (Mn4CaO5) cluster in the oxygen-evolving complex3-7. This reaction is coupled to the two-step reduction and protonation of the mobile plastoquinone QB at the acceptor side of PSII. Here, using serial femtosecond X-ray crystallography and simultaneous X-ray emission spectroscopy with multi-flash visible laser excitation at room temperature, we visualize all (meta)stable states of Kok's cycle as high-resolution structures (2.04-2.08 Å). In addition, we report structures of two transient states at 150 and 400 µs, revealing notable structural changes including the binding of one additional 'water', Ox, during the S2→S3 state transition. Our results suggest that one water ligand to calcium (W3) is directly involved in substrate delivery. The binding of the additional oxygen Ox in the S3 state between Ca and Mn1 supports O-O bond formation mechanisms involving O5 as one substrate, where Ox is either the other substrate oxygen or is perfectly positioned to refill the O5 position during O2 release. Thus, our results exclude peroxo-bond formation in the S3 state, and the nucleophilic attack of W3 onto W2 is unlikely.

The role of URO17® in diagnosis and follow up of bladder cancer patients.

OBJECTIVE: to evaluate the role of urinary URO17® biomarker in the detection of urothelial tumors in haematuria patients and the detection of recurrence in non-muscle invasive bladder urothelial tumors. MATERIALS AND METHODS: Our study was formed of two cohorts of patients, group I represents patients presenting with haematuria (n = 98), while group II represents patients with known non-muscle invasive bladder cancers on their scheduled follow up cystoscopic investigation (n = 51). For both groups, patients were asked to provide urine samples before cystoscopy, either primary as part of the haematuria investigation or as a scheduled follow-up. Urine samples were sent anonymously for standard urine cytology and URO17® biomarker immunostaining. Results were compared to cystoscopic findings using Chi-square analysis and Fisher's exact test (P < 0.05). RESULTS: Group I was formed of 98 patients, with an average age of 60 years. URO17® showed 100% sensitivity and 96.15% specificity with a negative predictive value (NPV) of 100 and a positive predictive value (PPV) of 95.83. The results showed statistical significance with P value < 0.001. Group II was formed of 51 patients, with an average age of 75 years. URO17® was shown to have a sensitivity of 85.71% and NPV of 95.45. Eleven patients of group II were on scheduled BacillusCalmette-Guerin (BCG) and another 5 received Mitomycin C (MMC). The overall results of both groups combined (n = 149) showed statistical significance between flexible cystoscopy results and the results of urinary URO17® and urine cytology. CONCLUSION: URO17® has a potential to be a reliable test for diagnosis and follow up of urothelial cancer patients and a screening tool adjunct to flexible cystoscopy. TRIAL REGISTRATION: Not applicable as the current study is not a clinical trial, as per according to the National Institutes of Health, "studies that involve a comparison of methods and that do not evaluate the effect of the interventions on the participant do not meet the NIH clinical trial definition."

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

The role of Aeromonas genotyping in virulence for Dicentrarchus labrax.

Aeromonas septicemia still represents a serious challenge facing the global aquaculture sector. In the present study, Aeromonas caviae and A. veronii were isolated from four diseased European seabass (Dicentrarchus labrax) farms experiencing a high mortality rate. Diseased fish showed haemorrhages on the external body surface with exophthalmia, cataracts, scale desquamation, skin ulcers and fin erosions. The most common post-mortem findings were congested internal organs, particularly the liver and posterior kidney. Twenty-eight A. Veronii and 11 A. caviae isolates were identified biochemically by the Vitek 2 system and then confirmed by PCR and phylogenetic analysis. Hemolysin (hlyA) and aerolysin (aer) were the most abundant virulence genes in the recovered isolates, followed by cytotoxic enterotoxin (act) and heat-stable enterotoxin (ast). A. caviae was more virulent than A. veronii for D. labrax fingerlings as LD50 ranging between (>1 × 108 -6.2 × 107 ) for A. veronii and (2.9 × 107 -8.3 × 107 ) for A. caviae. The sensitivity test indicated the effectiveness of norfloxacin, doxycycline and oxytetracycline against the tested isolates. Serum cortisol significantly increased in the infected groups, while catalase and glutathione peroxidase activities significantly decreased at 2 days post-infection (DPI) and then increased at 6 DPI. The presence of virulence genes was associated with bacterial pathogenicity expressed in fish mortality rate. Virulence genes also drastically affect cortisol levels more than catalase and glutathione peroxidase levels.

Outcomes of primary versus conversional Roux-En-Y gastric bypass after laparoscopic sleeve gastrectomy: a retrospective propensity score-matched cohort study.

BACKGROUND: Conversional surgery is common after laparoscopic sleeve gastrectomy (LSG) because of suboptimal weight loss (SWL) or poor responders and gastroesophageal reflux disease (GERD). Roux-en-Y gastric bypass (RYGB) is the most common conversional procedure after LSG. METHODS: A retrospective cohort study analyzed patients who underwent primary RYGB (PRYGB) or conversional RYGB (CRYGB) at three specialized bariatric centers between 2008 and 2019 and tested for weight loss, resolution of GERD, food tolerance (FT), early and late complications, and the resolution of associated medical problems. This was analyzed by propensity score matching (PSM). RESULTS: In total, 558 (PRYGB) and 155 (CRYGB) completed at least 2 years of follow-up. After PSM, both cohorts significantly decreased BMI from baseline (p < 0.001). The CRYGB group had an initially more significant mean BMI decrease of 6.095 kg/m2 at 6 months of follow-up (p < 0.001), while the PRYGB group had a more significant mean BMI decrease of 5.890 kg/m2 and 8.626 kg/m2 at 1 and 2 years, respectively (p < 0.001). Food tolerance (FT) improved significantly in the CRYGB group (p < 0.001), while CRYGB had better FT than PRYGB at 2 years (p < 0.001). A GERD resolution rate of 92.6% was recorded in the CRYGB (p < 0.001). Both cohorts had comparable rates of early complications (p = 0.584), late complications (p = 0.495), and reoperations (p = 0.398). Associated medical problems at 2 years significantly improved in both cohorts (p < 0.001). CONCLUSIONS: CRYGB is a safe and efficient option in non- or poor responders after LSG, with significant weight loss and improvement in GERD. Moreover, PRYGB and CRYGB had comparable complications, reoperations, and associated medical problem resolution rates.

Machine learning prediction of hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the United States.

BACKGROUND AND PURPOSE: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics. MATERIALS AND METHODS: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP). RESULTS: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone. CONCLUSION: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation.

Remediation through the coordinated use of local rice husk residues for the selective adsorption of iron and nickel in real landfill leachate.

Herein, we demonstrate the prospects of tackling several environmental problems by transforming a local rice husk residue into an effective adsorbent, which was then applied for the treatment of real landfill leachate (LL). The study focused on establishing (i) the effect of simple washing on morphological aspects, (ii) evaluating target adsorption capacity for total iron (Fe) and nickel (Ni), (iii) determining regeneration and reuse potential of the adsorbent and (iv) complying to the requirements of worldwide legislations for reuse of treated LL wastewater. The adsorbent was prepared by employing a simple yet effective purification process that can be performed in situ. The LL was collected post-membrane treatment, and the characterizations revealed high concentrations of Fe, Ni, and organic matter content. The simple washing affected the crystallinity, resulting in structural alterations of the adsorbents, also increasing the porosity and specific surface. The adsorption process for Ni occurred naturally at pH 6, but adjusting the pH to 3 significantly improved removal efficiency and adsorption capacity for total Fe. The kinetics were accurately described by the pseudo-second-order model, while the Langmuir model provided a better fit for the isotherms. The adsorbent was stable for 5 reuses, and the metals adsorbed were recovered through basic leaching. The removal capacities achieved underscore the remarkable effectiveness of the process, ensuring the treated LL wastewater meets rigorous global environmental legislations for safe use in irrigation. Thus, by employing the compelling methods herein optimized it is possible to refer to the of solving three environmental problems at once.

Formulation and evaluation of Fluconazole Nanosuspensions: In vitro characterization and transcorneal permeability studies.

The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 µm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.

The "foothill" entry for cephalomedullary nailing in unstable proximal femoral fractures: a technical note with a review of the literature.

Cephalomedullary nailing for unstable proximal femoral fractures is widely utilized, especially for geriatric osteoporotic fractures. There are two starting points for entry, namely trochanteric tip entry and pyriformis fossa entry, both have advantages and disadvantages, the tip of the greater trochanter seems that it is not the ideal starting point for trochanteric entry nails, the study presents the foothill entry point as a reproducible, technically feasible entry point to overcome the shortcoming of both standard starting points, and it could be easy executed with clear intraoperative fluoroscopic landmarks and lead to appropriate nail position without intraoperative complications.