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Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance. This prospective study investigated the equilibrium between memory T cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant recipients with operational tolerance (N=8), chronic rejection (N=8), and different immunosuppressive treatment regimens (N=81). Patients on hemodialysis and healthy individuals served as controls (N=50). In addition, the expression of Treg- and Breg-associated molecule genes was analyzed. Patients with chronic rejection showed a disrupted memory T cell composition with a significantly higher frequency of circulating CD8(+) terminally differentiated effector memory (TEMRA) T cells than patients with operational tolerance, patients on hemodialysis, or healthy controls (P<0.001). Low frequency of CD8(+) TEMRA and high frequency of Tregs and transitional Bregs were found in operationally tolerant patients. Consequently, operationally tolerant patients showed, as compared to all other transplant recipients with different immunosuppressive regiments, the lowest ratios between CD8(+) TEMRA T cells and Tregs or Bregs (for both P<0.001). Moreover, a specific peripheral blood transcription pattern was found in operationally tolerant patients with an increased expression of Breg- and Treg-associated genes CD22 and FoxP3 and a decreased Fc gamma RIIA/Fc gamma RIIB transcript ratio (for all P<0.001). In conclusion, monitoring the balance between circulating CD8(+) TEMRA T cells and regulatory cell subsets and their transcripts may help to distinguish transplant recipients with operational tolerance from recipients at risk of graft loss., European Union (EU); Horizon 2020; Research and Innovation Programme; Physician Scientist Program of the Heidelberg Faculty of Medicine; Olympia-Morata Program of the Heidelberg Faculty of Medicine

Kidney transplantation, the gold-standard therapeutic approach for patients with end-stage kidney disease, offers improvement in patient survival and quality of life. However, broad sensitization against human leukocyte antigens often resulting in a positive crossmatch against the patient's living donor or the majority of potential deceased donors in the allocation system represents a major obstacle due to a high risk for antibody-mediated rejection, delayed graft function and allograft loss. Kidney-paired donation and desensitization protocols have been established to overcome this obstacle, with limited success. Imlifidase, a novel immunoglobulin G (IgG)-degrading enzyme derived from Streptococcus pyogenes and recombinantly produced in Escherichia coli, is a promising agent for recipients with a positive crossmatch against their organ donor with high specificity towards IgG, rapid action and high efficacy in early pre-clinical and clinical studies. However, the rebound of IgG after a few days can lead to antibody-mediated rejection, making the administration of potent immunosuppressive regimens in the early post-transplant phase necessary. There is currently no comparative study evaluating the efficiency of imlifidase therapy compared with conventional desensitization protocols along with the lack of randomized control trials, indicating the clear need for future large-scale clinical studies in this field. Besides providing a practical framework for the clinical use of the agent, our aim in this article is to evaluate the underlying mechanism of action, efficiency and safety of imlifidase therapy in immunologically high-risk kidney transplant recipients., European Union (EU); Horizon 2020; Research and Innovation Programme

HLA-B*39:199 differs from HLA-B*39:10:01 by a G -> A substitution in exon 5 in codon 282., European Union (EU); Horizon 2020; Research and Innovation Programme

Colloidal nanocrystals (NCs) exhibit significant potential for photovoltaic bioelectronic interfaces because of their solution processability, tunable energy levels, and inorganic nature, lending them chemical stability. Silver bismuth sulfide (AgBiS2) NCs, free from toxic heavy-metal elements (e.g., Cd, Hg, and Pb), particularly offer an exceptional absorption coefficient exceeding 10(5) cm(-1) in the near-infrared (NIR), surpassing many of their inorganic counterparts. Here, we integrated an ultrathin (24 nm) AgBiS2 NC layer into a water-stable photovoltaic bioelectronic device architecture that showed a high capacitive photocurrent of 2.3 mAcm(-2) in artificial cerebrospinal fluid (aCSF) and ionic charges over 10 mu Ccm(-2) at a low NIR intensity of 0.5 mWmm(-2). The device without encapsulation showed a halftime of 12.5 years under passive accelerated aging test and did not show any toxicity on neurons. Furthermore, patch-clamp electrophysiology on primary hippocampal neurons under whole-cell configuration revealed that the device elicited neuron firing at intensity levels more than an order of magnitude below the established ocular safety limits. These findings point to the potential of AgBiS2 NCs for photovoltaic retinal prostheses., European Union (EU); Horizon Europe; European Research Council (ERC); MESHOPTO; Scientific and Technological Research Council of Turkey (TÜBİTAK); Fundació Joan Ribas Araquistain (FJRA); Fundació Privada Cellex, CERCA Program; “SeveroOchoa” Centre of Excellence

Semiconductor photocatalysis has recently emerged as a promising method for microbial inactivation. So far, quantum dots have generally been investigated as antibacterial suspension. Instead, here we demonstrate a InP/ZnS quantum dot nanoassembly film against both Gram-negative and Gram-positive bacteria. For effective operation in the solid phase, a thin layer of ZnS shell was grown on InP QD and the native long-chain ligand of stearic acid was replaced with sulfide that led to a high quantum yield of superoxide generation as 4.9%. QDs are assembled onto solid surfaces through sequential dip coating of positively charged poly(diallyldimethylammonium chloride) and negatively charged QDs. These QD nanoassemblies demonstrate growth inhibition against Escherichia coli and multidrug-resistant Staphylococcus aureus under illumination. Interestingly, such an approach can be directly applied to irregular surfaces, as well. This study unveils the potential of the nanoengineering of QDs for antibacterial coatings., European Union (EU); Horizon 2020; Research and Innovation Program; Marie Skłodowska-Curie Grant

Background: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female vs male heart transplant recipients. Methods: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988–2019, and subsequently combined using 2-stage individual patient data meta-analysis, to compare the excess risk of mortality in female vs male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age. Results: We analyzed 108,918 patients. When the donor was male, female recipients 0–12 years (Relative excess risk (RER) 1.13, 95% CI 1.00–1.26), 13–44 years (RER 1.17, 95% CI 1.10–1.25), and ≥45 years (RER 1.14, 95% CI 1.02–1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13–44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00–1.20), though not significantly (p = 0.05). Conclusions: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences., European Union (EU); Horizon 2020; Research and Innovation Programme; AV has accepted consulting fees and fellowship grant funding from Paladin Labs Inc. AM is supported by grants from the German Research Foundation (DFG; ME 3696/5-1 and ME3696/3-1) and the Lower Saxony Ministry of Science and Culture. GW is supported by NHMRC Investigator (APP 1195414) and Career Development Fellowship (APP 1147657). The authors declare no conflict of interest. RSP is supported by a Fonds de recherche du Quebec—Santé chercheur boursier clinician award (grant no. 254386), CIHR (grant FRN-156730) and fellowship grant funding from Paladin Labs Inc.

Background: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. Methods: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. Results: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. Conclusions: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss., European Union (EU); Horizon 2020; Research and Innovation Programme; A.J.V. has accepted consulting fees and fellowship grant funding from Paladin Labs Inc. A.M. is supported by grants from the German Research Foundation (DFG; ME 3696/5-1 and ME3696/3-1) and the Lower Saxony Ministry of Science and Culture. G.W. is supported by National Health and Medical Research Council Investigator (APP 1195414) and Career Development Fellowship (APP 1147657). R.S.-P. is supported by a Fonds de recherche du Quebec—Santé chercheur boursier clinician award (grant 254386) and Canadian Institutes of Health Research (grant FRN-156730). This study was supported by an operating grant from the Canadian Institutes of Health Research (PJT165832).

We report a case of antibody-mediated rejection treated with the human CD38 monoclonal antibody daratumumab in a 58-year-old female patient with end-stage kidney disease due to autosomal dominant polycystic kidney disease who received an ABO- and human leukocyte antigen antibody-incompatible living donor kidney transplant. The patient experienced an episode of severe antibody-mediated rejection within the first week of transplantation. Blood-group-antibody selective immunoadsorption in combination with administration of four doses of daratumumab (each 1800 mg s.c.) led to a persistent decrease of ABO- and more interestingly donor-specific human leukocyte antigen antibody reactivity and resulted in clinical and histopathological remission with full recovery of graft function, which has remained stable until post-transplant day 212. This case illustrates the potential of targeting CD38 in antibody-mediated rejection., European Union (EU); European Commission (EC); Horizon 2020; Research and Innovation Programme

We report herein a rationally designed metal-free ternary heterojunction, namely, black phosphorus quantum dots/ carbon nitride-reduced graphene oxide (BPQDs/CN-rGO), that functions as a photocatalyst in multiple photooxidation reactions including C=C bond cleavage, glycerol oxidation, and C-CF3 bond formation along with the removal of organic pollutants from wastewater. After the characterization of the structure and photophysical properties of BPQDs/CN-rGO heterojunction, it was first tested in the photodegradation of organic pollutants and showed superior performance. The underlying mechanism of BPQDs/CN-rGO in the photodegradation of organic pollutants revealed that the created internal electric field (IEF) among the components and photogenerated species (h+ and O-2(center dot-)) are attributed to superior activity. Prompted by these results, the BPQDs/CN-rGO photocatalyst was applied in other photooxidation reactions. The nonclassical-type-II heterojunction structure generates active species (O-2(center dot-), h(+), O-1(2)) under visible light irradiation, enabling the selective oxidation of glycerol to glyceric acid and C=C bond cleavage along with highly challenging Langlois reagent to heteroarenes., Scientific and Technological Research Council of Turkey (TÜBİTAK); Ph.D. Scholarship; Turkish Academy of Sciences (TU?BA); Council of Higher Education (YÖK)

What is this summary about? Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad((R))) compared with other oral treatments. What were the results? Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS. What do the results mean? The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS., Merck

Hydrogen sulfide (H2S) as a critical messenger molecule plays vital roles in regular cell function. However, abnormal levels of H2S, especially mitochondrial H2S, are directly correlated with the formation of pathological states including neurodegenerative diseases, cardiovascular disorders, and cancer. Thus, monitoring fluxes of mitochondrial H2S concentrations both in vitro and in vivo with high selectivity and sensitivity is crucial. In this direction, herein we developed the first ever example of a mitochondria-targeted and H2S-responsive new generation 1,2-dioxetane-based chemiluminescent probe (MCH). Chemiluminescent probes offer unique advantages compared to conventional fluorophores as they do not require external light irradiation to emit light. MCH exhibited a dramatic turn-on response in its luminescence signal upon reacting with H2S with high selectivity. It was used to detect H2S activity in different biological systems ranging from cancerous cells to human serum and tumor-bearing mice. We anticipate that MCH will pave the way for development of new organelle-targeted chemiluminescence agents towards imaging of different analytes in various biological models., Scientific and Technological Research Council of Turkey (TÜBİTAK)

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic anemia, intravascular hemolysis, and the occurrence of vaso-occlusive crises due to the mechanical obstruction of the microcirculation by poorly deformable red blood cells (RBCs). RBC deformability is a key factor in the pathogenesis of SCD, and is affected by various factors. In this study, we investigated the effects of adenylyl cyclase (AC) signaling pathway modulation and different phosphodiesterase (PDE) modulatory molecules on the deformability and mechanical stress responses of RBC from SCD patients (HbSS genotype) by applying 5 Pa shear stress with an ektacytometer (LORRCA). We evaluated RBC deformability before and after the application of shear stress. AC stimulation with Forskolin had distinct effects on RBC deformability depending on the application of 5 Pa shear stress. RBC deformability was increased by Forskolin before shear stress application but decreased after 5 Pa shear stress. AC inhibition with SQ22536 and protein kinase A (PKA) inhibition with H89 increased RBC deformability before and after the shear stress application. Non-selective PDE inhibition with Pentoxifylline increased RBC deformability. However, modulation of the different PDE types had distinct effects on RBC deformability, with PDE1 inhibition by Vinpocetine increasing deformability while PDE4 inhibition by Rolipram decreased RBC deformability after the shear stress application. The effects of the drugs varied greatly between patients suggesting some could benefit from one drug while others not. Developing drugs targeting the AC signaling pathway could have clinical applications for SCD, but more researches with larger patient cohorts are needed to identify the differences in the responses of sickle RBCs., Scientific and Technological Research Council of Turkey (TÜBİTAK)

The deployment of microneedles in biological fluid sampling and drug delivery is an emerging field in biotechnology, which contributes greatly to minimally-invasive methods in medicine. Prior studies on microneedles proposed designs based on the optimization of physical parameters through trial-and-error method. While these methods showed adequate results, it is possible to enhance the performance of a microneedle using a large dataset of parameters and their respective performance using advanced data analysis methods. Machine Learning (ML) offers the ability to mimic human learning behavior to expedite decision-making processes in biotechnology. In this study, the finite element analysis and ML models are combined to determine the optimal physical parameters for a microneedle design to maximize the amount of collected biological fluid. The fluid behavior in a microneedle patch is modeled using COMSOL Multiphysics (R), and the model is simulated with a set of initial physical and geometrical parameters in MATLAB (R) using LiveLink (TM). The mathematical model is used as the input to MATLAB's Bayesian Optimization function (bayesopt) and optimized for the maximum volumetric flow rate with pre-defined number of iterations. Within the parameter bounds, maximum volumetric flow rate is determined to be 21.16 mL min-1, which is 60% higher with respect to a system, where geometrical parameters are chosen randomly on average. This study introduces an online method for designing microneedles, where user can define the upper and lower bounds of the parameters to obtain an optimal design. The deployment of microneedles in biological fluid sampling and drug delivery is an emerging field in biotechnology, which contributes greatly to minimally-invasive methods in medicine., Scientific and Technological Research Council of Turkey (TÜBİTAK); TÜBİTAK 2232 International Fellowship for Outstanding Researchers Award; European Union (EU); Marie Sk?odowska-Curie Individual Fellowship; Alexander von Humboldt Research Fellowship for Experienced Researchers, and Royal Academy Newton-Katip Çelebi Transforming Systems Through Partnership award for financial support of this research. This work was partially supported by Science Academy's Young Scientist Awards Program (BAGEP), Outstanding Young Scientists Awards (GEBİP), and Bilim Kahramanlari Dernegi The Young Scientist Award.

The science of microrobots is accelerating towards the creation of new functionalities for biomedical applications such as targeted delivery of agents, surgical procedures, tracking and imaging, and sensing. Using magnetic properties to control the motion of microrobots for these applications is emerging. Here, 3D printing methods are introduced for the fabrication of microrobots and their future perspectives are discussed to elucidate the path for enabling their clinical translation., Scientific and Technological Research Council of Turkey (TÜBİTAK); 2232 International Fellowship for Outstanding Researchers Award; European Union (EU); Horizon 2020; Marie Skłodowska-Curie Individual Fellowship; Alexander von Humboldt Research Fellowship for Experienced Researchers, and Royal Academy Newton-Katip Çelebi Transforming Systems Through Partnership Award (120N019) for financial support of this research. This work was partially supported by Science Academy’s Young Scientist Awards Program (BAGEP), Outstanding Young Scientists Awards (GEBİP), and Bilim Kahramanlari Dernegi The Young Scientist Award. This study was conducted using the service and infrastructure of Koç University Translational Medicine Research Center (KUTTAM).

Introduction: Rejection remains the main cause of allograft failure in paediatric kidney transplantation and is driven by donor-recipient HLA mismatching. Modern computational algorithms enable assessment of HLA mismatch immunogenicity at the molecular level (molecular-mismatch, molMM). Whilst molMM has been shown to correlate with alloimmune outcomes, evidence demonstrating improved prediction performance against traditional antigen mismatching (antMM) is lacking. Methods: We analysed 177 patients from the CERTAIN registry (median follow-up 4.5 years). molMM scores included Amino-Acid-Mismatch-Score (AAMS), Electrostatic-Mismatch-Score (EMS3D) and netMHCIIpan (netMHC1k: peptide binding affinity <= 1000 nM; netMHC: binding affinity <= 500 nM plus rank <2%). We stratified patients into high/low-risk groups based on risk models of DSA development. Results: Donor-specific HLA antibodies (DSA) predominantly targeted the highest scoring molMM donor antigen within each HLA locus. MolMM scores offered superior discrimination versus antMM in predicting de novo DSA for all HLA loci; the EMS3D algorithm had particularly consistent performance (area under the receiver operating characteristic curve (AUC) >0.7 for all HLA loci vs. 0.52-0.70 for antMM). ABMR (but not TCMR) was associated with HLA-DQ molMM scores (AAMS, EMS3D and netMHC). Patients with high-risk HLA-DQ molMM had increased risk of graft function deterioration (50% reduction in baseline eGFR (eGFR50), adjusted HR: 3.5, 95% CI 1.6-8.2 high vs. low EMS3D). Multivariable modelling of the eGFR50 outcome using EMS3D HLA-DQ stratification showed better discrimination (AUC EMS3D vs. antMM at 2 years: 0.81 vs. 0.77, at 4.5 years: 0.72 vs. 0.64) and stratified more patients into the low-risk group, compared to traditional antMM. Conclusion: Molecular mismatching was superior to antigen mismatching in predicting humoral alloimmunity. Molecular HLA-DQ mismatching appears to be a significant prognostic factor for graft functio, European Union (EU); Horizon 2020; Research and Innovation Programme; The CERTAIN registry received funding from Astellas and Novartis. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. All authors declare no other competing interests. The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN) and The German Society for Paediatric Nephrology (GPN). JKi acknowledges funding from a MRC NIHR fellowship (MR/V037900/1). VK acknowledges funding from an NIHR Fellowship (PDF-2016-09-065) and as a Paul I. Terasaki Scholar. VK acknowledges funding from the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU, Grant number: NIHR203332) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health or National Health Service Blood and Transplant.

Donor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and December 2022 to validate the clinical value of dd-cfDNA in a cohort of German patients. dd-cfDNA was quantified at biopsy and correlated to histopathology. Additionally, dd-cfDNA was determined on days 7, 30, and 90 post-biopsy and analyzed for potential use to monitor response to anti-rejection treatment. dd-cfDNA levels were with a median (IQR) % of 2.00 (0.48-3.20) highest in patients with ABMR, followed by 0.92 (0.19-11.25) in patients with TCMR, 0.44 (0.20-1.10) in patients with borderline changes and 0.20 (0.11-0.53) in patients with no signs of rejection. The AUC for dd-cfDNA to discriminate any type of rejection including borderline changes from no rejection was at 0.72 (95% CI 0.62-0.83). In patients receiving anti-rejection treatment, dd-cfDNA levels significantly decreased during the 7, 30, and 90 days follow-up compared to levels at the time of biopsy (p = 0.006, p = 0.002, and p < 0.001, respectively). In conclusion, dd-cfDNA significantly discriminates active rejection from no rejection. Decreasing dd-cfDNA following anti-rejection treatment may indicate response to therapy., European Union (EU); Horizon 2020; Research and Innovation Programme; LB is funded by the Olympia Morata Program of Heidelberg University. CSp is funded by the Physician Scientist Program of the Heidelberg Faculty of Medicine. For the publication fee we acknowledge financial support by Deutsche Forschungsgemeinschaft within the funding program “Open Access Publikationskosten” as well as by Heidelberg University.

Black phosphorus (BP) has recently emerged as a versatile photocatalyst owing to its unique photophysical properties and tunable bandgap. Nonetheless, the rapid recombination of the photogenerated charges of pristine BP samples has significantly hindered its practical applications in photocatalysis. Herein, we report, for the first time, the effect of transition metal nanoparticles (Ni and Co) as co-catalysts on the photocatalytic activity of BP/tungsten disulfide (WS2) binary heterojunctions (BP/WS2-TM (TM: Ni, Co)) in the hydrogen evolution reaction (HER) under visible light irradiation (& lambda; > 420 nm). Ternary heterojunctions named BP/WS2-TM (TM: Ni, Co) were synthesized via a chemical reduction method, leading to the formation of an S-scheme heterojunction, in which BP acts as a reduction catalyst and WS2 serves as an oxidation catalyst. BP/WS2-Ni and BP/WS2-Co performed substantial amounts of hydrogen generation of 9.53 mmol h(-1)g(-1) and 12.13 mmol h(-1)g(-1), respectively. Moreover, BP/WS2-Co exhibited about 5 and 15 times higher photocatalytic activity compared to the binary BP/WS2 heterojunctions and pristine BP, respectively. The enhanced photocatalytic activity of the heterojunction catalysts is attributed to the extended light absorption ability, enhanced charge separation, and larger active sites. This study is the first example of photocatalytic hydrogen evolution from water by using Ni- and Co-doped binary BP/WS2 heterojunctions., Scientific and Technological Research Council of Turkey (TÜBİTAK); Selcuk University Scientific Research Projects

In this study, we aimed to investigate the changes in the B cell subpopulations after homologous or heterologous COVID-19 boosters. Blood samples were collected after baseline (3-5 months after two doses of CoronaVac), 1 and 3 months after BNT162b2 (n=28 and n=6), and CoronaVac (n=7 and n=4) boosters. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with B cell markers, the ratios of naive (CD19+CD20+CD27-), memory (CD19+CD20+CD27+), memory B cells expressing IgG (CD19+CD20+CD27+IgG+), and effector memory B cells (CD19+CD20+CD27+CD38+) were identified with flow cytometry. Significantly higher expression of memory B cells was observed in one month with BNT162b2 (12.16% one month, 5.98% three months) and CoronaVac (14.18% one month, 9.00% three months) boosters. IgG expressing memory B cell expression was significantly higher with BNT162b2 than with CoronaVac booster in one month (22.70% and 13.95%, respectively). The ratio of effector B cells in the first month after CoronaVac booster (25.44%) was significantly higher than the BNT162b2 booster (9.90%, p=0.0263)., This study was supported by Koç University İşBank Research Center for Infectious Diseases (KUISCID).

A 57-year-old female patient presented with fever, nausea, vomiting, loss of appetite, and weight loss within the last two months. Ceftriaxone and metronidazole therapy was start-ed upon discovery of a liver abscess but provided no benefit. Following the of abscess bi-opsy, the patient developed fever, itching, anemia, acute renal failure, hyperbilirubinemia, and eosinophilia that required intensive care unit (ICU) admission. The Fasciola hepatica antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Triclabendazole was started, after which the symptoms and magnetic resonance imaging (MRI) findings regressed. Even without eosinophilia, F. hepatica should be considered in cases with a liver abscess that does not respond to antibiotics., NA

We aimed to describe the increased rate of Acinetobacter baumannii infections during the COVID-19 pandemic and define its significance within the last five years. This study was performed in a tertiary hospital with 280 beds and included all patients infected with A. baumannii in the intensive care unit between January 1, 2018, and June 30, 2022. A. baumannii-infected patients in the intensive care unit 27 months before the pandemic and 27 months during the pandemic were included. Pulsed-field gel electrophoresis was performed to assess clonal relatedness. The infection control measures were specified based on the findings and targeted elimination. In total, 5718 patients were admitted to the intensive care unit from January 1st, 2018, to June 30th, 2022. A. baumannii infection was detected in 81 patients. Compared to the pre-pandemic era, the rate of A. baumannii infection during the pandemic was 1.90 times higher (OR: 1.90, 95% CI: [1.197, 3.033]). Clonality assessment of multidrug-resistant A. baumannii samples revealed eight clusters with one main cluster comprising 14/27 isolates between 2021 and 2022. The case fatality rate of the pre-pandemic and pandemic era was not different statistically (83.33% vs. 81.48%, p=0.835). Univariate analysis revealed the association of mechanical ventilation (p=0.002) and bacterial growth in tracheal aspirate (p=0.001) with fatality. During the COVID-19 pandemic, potential deficits in infection control measures may lead to persistent nosocomial outbreaks. In this study, the introduction of enhanced and customized infection control measures has resulted in the containment of an A. baumannii outbreak., The consumables of this study were funded by Koc University IsBank Center for Infectious Diseases (KUISCID).

NA

Context: Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized. Objective: To investigate their morphologic, immunohistochemical, and molecular features. Design:Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing. Results: The mean age at diagnosis was 69 years (42–81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%). Conclusions: Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in, This work has been supported by a gift from the Melamed Family Foundation, and by the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748.

Considering the existence of a large number and variety of metal-organic frameworks (MOFs) and ionic liquids (ILs), assessing the gas separation potential of all possible IL/MOF composites by purely experimental methods is not practical. In this work, we combined molecular simulations and machine learning (ML) algorithms to computationally design an IL/MOF composite. Molecular simulations were first performed to screen approximately 1000 different composites of 1-n-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) with a large variety of MOFs for CO2 and N2 adsorption. The results of simulations were used to develop ML models that can accurately predict the adsorption and separation performances of [BMIM][BF4]/MOF composites. The most important features that affect the CO2/N2 selectivity of composites were extracted from ML and utilized to computationally generate an IL/MOF composite, [BMIM][BF4]/UiO-66, which was not present in the original material data set. This composite was finally synthesized, characterized, and tested for CO2/N2 separation. Experimentally measured CO2/N2 selectivity of the [BMIM][BF4]/UiO-66 composite matched well with the selectivity predicted by the ML model, and it was found to be comparable, if not higher than that of all previously synthesized [BMIM][BF4]/MOF composites reported in the literature. Our proposed approach of combining molecular simulations with ML models will be highly useful to accurately predict the CO2/N2 separation performances of any [BMIM][BF4]/MOF composite within seconds compared to the extensive time and effort requirements of purely experimental methods., NA

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease caused by a perturbed immune system. The scarcity of short- and long-term immune monitoring of AIH hampered us to comprehend the interaction between immunosuppressive medication and immune homeostasis. Methods and patients: We recruited children with AIH at the time of diagnosis and at the 1st, 3rd, 6th, 12th, 18th, and 24th months of immunosuppression (IS). We also enrolled children with AIH being on IS for >2 years. Children with drug-induced liver injury (DILI), and those receiving tacrolimus after liver transplantation (LT), were enrolled as disease/IS control subjects. Healthy children (HC) were also recruited. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Healthy liver tissue from adult donors and from livers without inflammation were obtained from children with hepatoblastoma. By using flow cytometry, we performed multi-parametric immune profiling of PBMCs and intrahepatic lymphocytes. Additionally, after IS with prednisolone, tacrolimus, rapamycin, or 6-mercaptopurine, we carried out an in vitro cytokine stimulation assay. Finally, a Lifecodes SSO typing kit was used to type HLA-DRB1 and Luminex was used to analyze the results. Results: Untreated AIH patients had lower total CD8 T-cell frequencies than HC, but these cells were more naive. While the percentage of naive regulatory T cells (Tregs) (CD4(+)FOXP3(low)CD45RA(+)) and regulatory B cells (Bregs, CD20(+)CD24(+)CD38(+)) was similar, AIH patients had fewer activated Tregs (CD4(+)FOXP3(high)CD45RA(-)) compared to HC. Mucosal-associated-invariant-T-cells (MAIT) were also lower in these patients. Following the initiation of IS, the immune profiles demonstrated fluctuations. Bregs frequency decreased substantially at 1 month and did not recover anymore. Additionally, the frequency of intrahepatic Bregs in treated AIH patients was lower, compared to control livers, DILI, and LT patients. Following in vitro IS, This project was funded by the Turkish Association for the Study of the Liver (TASL) charity, and seed funded by Koc University.

Two ionic liquids (ILs) having the same cation with different anions offering opposite hydrophilic/hydrophobic characters, 1-n-butyl-1-methylpyrrolidinium dicyanamide ([BMPyr][DCA]) and 1-n-butyl-1-methylpyrrolidinium hexafluorophosphate ([BMPyr][PF6]), were impregnated onto two different reduced graphene aerogels (rGAs) prepared by the thermal treatment of GAs at 300 and 500 degrees C to investigate the consequences of the changes in the hydrophilic character of ILs and the reduction temperature of the GAs on the corresponding gas sorption and separation performance of the IL/rGAs. The structural analyses of nanoporous rGAs and IL/rGAs pointed to a change in the quantity of oxygenated functional groups upon thermal treatment and a change in the direct interactions between IL molecules and the host rGA surface upon IL deposition. Single-component CO2 and CH4 sorption measurements were performed for each rGA and IL/rGA composite, and both ideal and mixture CO2/CH4 selectivities were calculated. The samples prepared by reducing the GA at 300 and 500 degrees C yielded ideal CO2/ CH4 selectivities of 3.6 and 18 at 1 mbar and 25 degrees C, respectively. Among IL/rGA composites, the one prepared at 300 degrees C displayed a remarkable CO2/CH4 separation performance when combined with the hydrophobic [BMPyr][PF6], offering an ideal selectivity of 450.9 at 1 mbar and 25 degrees C, whereas the composite prepared with rGA500 yielded a substantially high CO2/CH4 selectivity of 173.5 after the incorporation of the hydrophilic [BMPyr][DCA] at 1 mbar and 25 degrees C. The ideal CO2/CH4 selectivities of [BMPyr][PF6]/ rGA300 and [BMPyr][DCA]/rGA500 surpassed most of the previously reported selectivities of carbon-based materials in the literature. These results demonstrate the broad potential of IL/rGAs in sorption-based gas separations owing to the highly tunable nature of both the structure of IL and the surface characteristics of rGA., Scientific and Technological Research Council of Turkey (TÜBİTAK)

Solvent-free polymer-based electrolytes (SPEs) have gained significant attention to realize safer and flexible lithium-ion batteries. Among all polymers used for preparing SPEs electrolytes, poly(ethylene oxide), a biocompatible and biodegradable polymer, has been the most prevalent one mainly because of its high ionic conductivity in the molten state, the capability for the dissolution of a wide range of different lithium salts as well as its potential for the environmental health and safety. However, linear PEO is highly semicrystalline at room temperature and thus exhibits weak mechanical performance. Addition of nanoparticles enhances the mechanical strength and effectively decreases the crystallization of linear PEO, yet enhancement in mechanical performance often results in decreased ionic conductivity when compared to the neat linear PEO-based electrolytes; new strategies for decoupling ionic conductivity from mechanical reinforcement are urgently needed. Herein, we used lithium bis(trifluoromethane-sulfonyl)-imide (LiTFSI) salts dissolved in various nonlinear PEO architectures, including stars (4-arms and 8-arms) and hyperbranched matrices, and SiO2 nanoparticles (approximately equal to 50 nm diameter) as fillers. Compared to the linear PEO chains, the room temperature crystallinity was eliminated in the branched PEO architectures. The electrolytes with good dispersion of the nanoparticles in the nonlinear PEOs significantly enhanced ionic conductivity, specifically by approximately equal to 40% for 8-arm star, approximately equal to 28% for 4-arms star, and approximately equal to %16 for hyperbranched matrices, with respect to the composite electrolyte with the linear matrix. Additionally, the rheological results of the SPEs with branched architectures show more than three orders of magnitude enhancement in the low-frequency moduli compared to the neat linear PEO/Li systems. The obtained results demonstrate that the solvent-free composite electrolytes made, This work is supported by Turkish Academy of Sciences Distinguished Young Scientist Award (TÜBA GEBİP) Program. The authors also acknowledge the Central Research Infrastructure Directorate at Koç University for the use of BDS services. We thank Asst. Prof. Umut Aydemir for use of the glove box for the electrolyte preparation. We are also grateful to Assoc. Prof. Sedat Nizamoğlu for the use of electrochemical impedance spectrometer. We also acknowledge Dr. Hadi Jahangiri for their assistance on the XRD measurements.