bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycosynthesis of silver nanoparticles from endophytic Aspergillus flavipes AUMC 15772: ovat-statistical optimization, characterization and biological activities
Authors: EL-Zawawy Nessma A. , Abou-Zeid Alaa M. , Beltagy Doha M. , Hantera Nada H. , Nouh Hoda S. 
Published: November 2023

Abstract
Background
Mycosynthesis of silver nanoparticles (SNPs) offers a safe, eco-friendly, and promising alternative technique for large-scale manufacturing. Our study might be the first report that uses mycelial filtrate of an endophytic fungus, Aspergillus flavipes, for SNPs production under optimal conditions as an antimicrobial agent against clinical multidrug-resistant (MDR) wound pathogens.

Results
In the present study, among four different endophytic fungi isolated from leaves of Lycium shawii, the only one isolate that has the ability to mycosynthesize SNPs has been identified for the first time as Aspergillus flavipes AUMC 15772 and deposited in Genebank under the accession number OP521771. One variable at a time (OVAT) and Plackett Burman design (PBD) were conducted for enhancing the production of mycosynthesized SNPs (Myco-SNPs) through optimization using five independent variables. The overall optimal variables for increasing the mycosynthesis of SNPs from mycelial filtrate of A. flavipes as a novel endophytic fungus were a silver nitrate concentration of 2 mM, a pH of 7.0, an incubation time of 5 days, and a mycelial filtrate concentration of 30% in dark conditions. UV–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray spectroscopy (XRD), Transmission electron microscopy (TEM), and Selected-Area Electron Diffraction (SAED) patterns were used to characterize Myco-SNPs, which showed the peak of absorbance at 420 nm, and FTIR showed the bands at 3426.44, 2923.30, 1681.85, 1552.64, and 1023.02 cm-1, respectively, which illustrated the presence of polyphenols, hydroxyl, alkene, nitro compounds, and aliphatic amines, respectively. The XRD pattern revealed the formation of Myco-SNPs with good crystal quality at 2θ = 34.23° and 38.18°. The TEM image and SAED pattern show the spherical crystalline shape of Myco-SNPs with an average size of 6.9232 nm. High antibacterial activity of Myco-SNPs was recorded against MDR wound pathogens as studied by minimum inhibitory concentrations ranging from 8 to 32 µg/mL, time kill kinetics, and post-agent effects. Also, in vitro cell tests indicated that Myco-SNPs support the cell viability of human skin fibroblast cells as a nontoxic compound.

Conclusion
The obtained results revealed the successful production of Myco-SNPs using the mycelial filtrate of A. flavipes, which may be a promising nontoxic alternative candidate for combating MDR wound pathogens.
Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis
Authors: Huang Shuang , Zheng Gang , Yang Kai 
Published: November 2023

Abstract
Background
The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors.

Methods
This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software.

Results
A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3–4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3–4 adverse events in patients (P < 0.05).

Conclusions
As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3–4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.
Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier
Authors: Holst Mikkel Roland , de Wit Nienke Marije , Ozgür Burak , Brachner Andreas , Hyldig Kathrine , Appelt-Menzel Antje , Sleven Hannah , Cader Zameel , de Vries Helga Eveline , Neuhaus Winfried , Jensen Allan , Brodin Birger , Nielsen Morten Schallburg 
Published: November 2023

AbstractHere, we report an experimental setup to benchmark different receptors for targeted therapeutic antibody delivery at the blood–brain barrier. We used brain capillary endothelial-like cells derived from induced pluripotent stem cells (hiPSC-BECs) as a model system and compared them to colon epithelial Caco-2 cells. This approach helped to identify favourable receptors for transport into the cell layer itself or for directing transport for transcytosis across the cell layer. The sorting receptors transferrin receptor and sortilin were shown to be efficient as antibody cargo receptors for intracellular delivery to the cell layer. In contrast, the cell surface receptors CD133 and podocalyxin were identified as static and inefficient receptors for delivering cargo antibodies. Similar to in vivo studies, the hiPSC-BECs maintained detectable transcytotic transport via transferrin receptor, while transcytosis was restricted using sortilin as a cargo receptor. Based on these findings, we propose the application of sortilin as a cargo receptor for delivering therapeutic antibodies into the brain microvascular endothelium.
Graphical Abstract
Clinical outcomes during and beyond different COVID-19 critical illness variant periods compared with other lower respiratory tract infections
Authors: Hedberg Pontus , Baltzer Nicholas , Granath Fredrik , Fored Michael , Mårtensson Johan , Nauclér Pontus 
Published: November 2023

Abstract
Background
It is yet to be better understood how outcomes during and after the critical illness potentially differ between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from other lower respiratory tract infections (LRTIs). We aimed to compare outcomes in adults admitted to an intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) during the Wild-type, Alpha, Delta, and Omicron periods with individuals admitted with other LRTI.

Methods
Population-based cohort study in Stockholm, Sweden, using health registries with high coverage, including ICU-admitted adults from 1 January 2016 to 15 September 2022. Outcomes were in-hospital mortality, 180-day post-discharge mortality, 180-day hospital readmission, 180-day days alive and at home (DAAH), and incident diagnoses registered during follow-up.

Results
The number of ICU admitted individuals were 1421 Wild-type, 551 Alpha, 190 Delta, 223 Omicron, and 2380 LRTI. In-hospital mortality ranged from 28% (n = 665) in the LRTI cohort to 35% (n = 77) in the Delta cohort. The adjusted cause-specific hazard ratio (CSHR) compared with the LRTI cohort was 1.33 (95% confidence interval [CI] 1.16–1.53) in the Wild-type cohort, 1.53 (1.28–1.82) in the Alpha cohort, 1.70 (1.30–2.24) in the Delta cohort, and 1.59 (1.24–2.02) in the Omicron cohort. Among patients discharged alive from their COVID-19 hospitalization, the post-discharge mortality rates were lower (1–3%) compared with the LRTI cohort (9%), and the risk of hospital readmission was lower (CSHRs ranging from 0.42 to 0.68). Moreover, all COVID-19 cohorts had compared with the LRTI cohort more DAAH after compared with before the critical illness.

Conclusion
Overall, COVID-19 critical was associated with an increased hazard of in-hospital mortality, but among those discharged alive from the hospital, less severe long-term outcomes were observed compared with other LRTIs.
Quantification of evolved DNA-editing enzymes at scale with DEQSeq
Authors: Schmitt Lukas Theo , Schneider Aksana , Posorski Jonas , Lansing Felix , Jelicic Milica , Jain Manavi , Sayed Shady , Buchholz Frank , Sürün Duran 
Published: November 2023

AbstractWe introduce DEQSeq, a nanopore sequencing approach that rationalizes the selection of favorable genome editing enzymes from directed molecular evolution experiments. With the ability to capture full-length sequences, editing efficiencies, and specificities from thousands of evolved enzymes simultaneously, DEQSeq streamlines the process of identifying the most valuable variants for further study and application. We apply DEQSeq to evolved libraries of Cas12f-ABEs and designer-recombinases, identifying variants with improved properties for future applications. Our results demonstrate that DEQSeq is a powerful tool for accelerating enzyme discovery and advancing genome editing research.
Channel state information-based wireless localization by signal reconstruction
Authors: Hu Yunbing , Peng Ao , Li Shenghong , Tang Biyu , Ni Wei , Lu Xianzhi , Tang Jianguo 
Published: November 2023

AbstractWireless localization technology has been widely used in indoor and outdoor fields. Channel estimation based on channel state information is a hot research topic in recent years. However, due to the interference of acquisition bandwidth, noise and Doppler effect, high-resolution channel estimation is a difficult problem. In this paper, the least squares estimate the amplitude of the signal subspace projection and estimate the time delay, using wireless channel state information to delay obey exponential distribution and magnitude obey normal distribution features, and reconstruction after the signal space and sampling to the Euclidean distance between the signal space, common as gradient optimization parameters, estimate the arrival time delay of high precision. The algorithm proposed in this paper filters out the noise interference in wireless communication and improves the accuracy of channel estimation through the method of least square and gradient optimization, which provides a feasible scheme for indoor wireless localization.
Local adiposity may be a more reliable predictor for infection than body mass index following total knee arthroplasty: a systematic review
Authors: Heifner John J. , Sakalian Philip A. , Rowland Robert J. , Corces Arturo 
Published: November 2023

AbstractPurposeImproved understanding of the factors that predispose TKA patients to infection has considerable economic and medical impact. BMI is commonly used as a proxy for obesity to determine the risk of postoperative infection. However, this metric appears to be fraught with inconsistency in this application. BMI is a simple calculation which provides general insight into body habitus. But it fails to account for anatomic distribution of adipose tissue and the proportion of the mass that is skeletal muscle. Our objective was to review the literature to determine if local adiposity was more predictive than BMI for infection following TKA.MethodsA database search was performed for the following PICO (Population, Intervention, Comparison, and Outcome) characteristics: local measurements of adiposity (defined as soft tissue thickness or fat thickness or soft tissue envelope at the knee) in patients over 18 years of age treated with total knee arthroplasty used to determine the relationship between local adiposity and the risk of infection (defined as prosthetic joint infection or wound complication or surgical site infection).Quality was assessed using the GRADE framework and bias was assessed using ROBINS‐I.ResultsSix articles (N=7081) met the inclusion criteria. Four of the six articles determined that adiposity was more associated with or was a better predictor for infection risk than BMI. One of the six articles concluded that increased adiposity was protective for short term infection and that BMI was not associated with the outcome of interest. One of the six articles determined that BMI was more strongly associated with PJI risk than soft tissue thickness.ConclusionThe use of adiposity as a proxy for obesity in preoperative evaluation of TKA patients is an emerging concept. Although limited by heterogeneity, the current literature suggests that local adiposity may be a more reliable predictor for infection than BMI following primary TKA.Level of evidenceIV systematic review
89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations
Authors: Kahts Maryke , Guo Hua , Kommidi Harikrishna , Yang Yanping , Sayman Haluk Burcak , Summers Beverley , Ting Richard , Zeevaart Jan Rijn , Sathekge Mike , Aras Omer 
Published: November 2023

Abstract
Background
The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium-89 (89Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood.

Results
The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30–60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered 89Zr-labelled leukocytes produced high-contrast murine PET images at 1 h–5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously 89Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [89Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo.

Conclusions
Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies.
Factors affecting job satisfaction among nurses working in Ondo state
Authors: Olaniyan Joseph Olawale , Adetunji Kemisola Mercy , Adetunji Ademola Abiodun 
Published: November 2023

AbstractThe level of satisfaction received on the job is highly essential in the discharge of duty. Nurses' respected level of job satisfaction improves turnover, commitment, and patient satisfaction. This study assesses factors affecting job satisfaction among nurses at the University of Medical Science Teaching Hospital, Ondo, Nigeria, to identify factors responsible for job satisfaction. The study utilizes the Index of Work Satisfaction with few modifications. Questionnaires were distributed to 154 sample respondents across different units of the hospital. Cronbach's Alpha is used to validate the internal consistency of the instrument. Data coding and cleaning were done using Microsoft Excel, and analysis was done with SPSS (version 23). The percentage is used to explore the responses. In contrast, independent sample t tests and one-way analysis of variance are used to assess variations across different sociodemographic groups of the respondents. Results show that higher percentages of the respondents are dissatisfied with their job because of issues relating to salary and benefits. Workload and Administrative & management bottlenecks also sometimes contribute to job dissatisfaction. Professional pride and colleague relationships are not significant factors that affect job satisfaction. To retain the best hands in the hospital, the management is advised to constantly look into issues relating to salary and benefits for the nurses. They are also advised to look into the processes and procedures for career advancement and pay upgrades in the hospital.
Diagnostic yield of combined ultrasound-guided fine needle aspiration and core needle biopsy versus either technique alone in peripheral lung and pleural lesions
Authors: Sweed Rania Ahmed , Khalil Yehia Mohamed , Sharawy Hany Amin , Alsawy Eman Sheta Ali Gawdat , Botros Mina 
Published: November 2023

Abstract
Introduction
Ultrasound (US) has become an integral tool for chest assessment as it provides crucial information on pleural pathologies and peripherally located lung lesions.

Aim
To assess the diagnostic yield of combined fine needle aspiration (FNAB) and core needle biopsy (CNB) versus each technique ultrasound-guided in peripheral lung and pleural lesions.

Methodology
The present study enrolled 30 patients presenting to Alexandria Main University Hospital, with CT scans showing undiagnosed peripheral lung or parietal pleural lesions with or without effusion. A full ultrasound chest assessment was done covering 12 regions. Assessment of the lesion of interest, vascularity was assessed via color Doppler, locating the safest entry site. Real-time US-guided FNAB was done using a spinal needle 22 gauge. Then real-time US-guided CNB using 18 gauge Trucut needle in the same setting. Duration and complications of each procedure were reported. In FNAB, three smears were prepared, fixed in alcohol, and stained with hematoxylin and eosin stain. The remaining sample was fixed in formalin and centrifuged to prepare cell blocks. On the other hand, Trucut needle biopsy specimens were fixed in formalin and processed as paraffin-embedded blocks. Immunohistochemical staining was done. The results were classified into four categories (inadequate, negative, suspicious, and positive for malignancy.

Results
The diagnostic yield of combined techniques was 96.7% versus 63.3% using FNAB and 96.7% using CNB. The sensitivity of FNAB was 86% while CNB was 95%. The specificity and positive predictive value of both methods were 100%. The negative predictive value of FNAB was 57% versus 80% for CNB in peripheral lung lesions. Duration of US-guided CNB was statistically significantly longer than that of FNAB in both peripheral lung and pleural lesions. No major complications were reported using either technique.

Conclusion
Combined FNAB and CNB were not superior to CNB alone regarding diagnostic yield but were superior to FNAB. Ultrasound-guided CNB has a superior diagnostic yield over FNAB, with no statistically significant difference regarding associated complications, both techniques are safe. FNAB provided sufficient material for ancillary molecular testing.
A fast algorithm for simulation and analysis of wavefields in acoustic single-well imaging of logging-while-drilling considering arbitrary types of sources
Authors: Xu Jiaqi , Hu Hengshan , Han Bo 
Published: November 2023

Acoustic single-well imaging (SWI) of logging-while-drilling (LWD) is an advanced logging method in reservoir exploration, which uses reflected waves to detect the around-borehole geologic structures and quickly determines the drilling direction for enhancing the drilling-encounter ratio and reducing the drilling risk. Forward acoustic modeling is a fundamental problem for SWI in LWD. Due to the complex structures, it is a challenge to simulate the wave propagation and investigate wavefield characteristics based on the forward model. Numerical modeling is a commonly used method for calculating wavefields; however, it is too computationally expensive. In this study, we develop a fast method for calculating the full reflected pressure and displacement waves (i.e., P-P, SV-SV, SH-SH, and P-SV/SV-P) in SWI of LWD considering different types of sources such as arcuate, monopole, and dipole transmitters. The analytical algorithm is developed by applying the reciprocity relation between the virtual force (displacement) sources located at the receiver position and the outside-borehole virtual forces that are equivalent to the reflections from the formation interfaces. Numerical experiments indicate that the analytical solutions agree well with the reference solutions from the 3D finite-difference time-domain method, demonstrating the accuracy and high efficiency of the analytical method. Based on the analytical solutions, we find that LWD reflected waves are much more sensitive to the azimuth than those in the wireline case, indicating that the availability of LWD is important for identifying the reflector azimuth. Furthermore, to enhance the reception efficiency of reflected waves, the LWD parameters are optimized. For slow formations, we suggest using a dipole source with dominant excitation-frequency band being from 1 kHz to 3 kHz. For fast formations, a dipole with wider excitation-frequency band from 1 kHz to 5 kHz is recommended. For all formations, recording pressure signals indicates much higher reception efficiency than the displacement signals.
Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children
Authors: Thornton Paul S , De Leon Diva D , Empting Susann , Zangen David , Kendall David M , Birch Sune , Bøge Eva , Ivkovic Jelena , Banerjee Indraneel 
Published: November 2023

Abstract

Context
Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion causing hypoglycemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI.

Objective
To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycemia as add-on to standard of care (SoC).

Methods
In this open-label trial, patients were randomized 1:1 to SoC or SoC + dasiglucagon (10-70 µg/h) for 4 weeks. In the following 4 weeks, all patients received dasiglucagon + SoC. Hypoglycemia was assessed by self-monitored plasma glucose (SMPG) and blinded continuous glucose monitoring (CGM). Primary endpoint was average number of SMPG-detected hypoglycemia episodes/week (SMPG &lt;3.9 mmol/L) during Weeks 2 to 4.

Results
Thirty-two patients (0.6-10.9 years) were randomly assigned to dasiglucagon + SoC (n = 16) or SoC (n = 16). The rate of SMPG-detected hypoglycemia decreased from baseline in both groups, but with no statistically significant difference during Weeks 2 to 4 (event rate ratio: 0.85 [0.54; 1.36], P = .5028). However, dasiglucagon administration resulted in a 43% reduction in CGM-detected hypoglycemia (&lt;3.9 mmol/L) vs SoC alone during Weeks 2 to 4 (post hoc analysis; event rate ratio: 0.57 [0.39; 0.83], P = .0029). Dasiglucagon enabled reductions (of 37% to 61%) in all other measures of hypoglycemia assessed by CGM vs SoC alone including extent and percent time in hypoglycemia (post hoc analyses). Dasiglucagon appeared safe and well tolerated. Skin and gastrointestinal events were more frequent with dasiglucagon + SoC than SoC only.

Conclusion
Clinically meaningful reductions in all CGM-recorded measures of hypoglycemia support using dasiglucagon as a potential treatment for CHI.