E. coli BSI.Several randomized controlled trials (RCT) have shown that short-course (∼7 days) antibiotic treatment is non-inferior to longer antibiotic courses (∼14 days) in patients with uncomplicated bloodstream infection (BSI) with mostly susceptible Gram-negative bacteria. Here, we evaluate short-course therapy in ceftriaxone-resistant E. coli BSI at 14 United States hospitals between November 2020 and April 2021, each patient with ceftriaxone-R E. coli BSI, and the next consecutive patient with a ceftriaxone-S E. coli BSI was included. Patients who received 5-8 days (“short”) or 9-21 days (“long”) of antibiotics were included in this analysis. Patients who died before day 9 were excluded. Primary outcome was a Desirability of Outcome Ranking  based on disposition at day 30 after collection of the index blood culture. Ceftriaxone susceptibility was centrally determined using broth microdilution for all bacterial isolates.In a prospective cohort of 300 patients with Desirability of outcome ranking (DOOR) categoriesOf 300 patients in the original cohort, 227 were included; 44 patients  received short , and 183 patients  received long duration . Age , sex , and Charlson comorbidity index  were similar between groups. Notably, almost all patients  with solid organ or stem cell transplant were in the long duration group. The median Pitt bacteremia score was 2 (IQR 1-3) in the short duration group vs. 1 (IQR 0-3) in the long duration group (Wilcoxon Rank Sum p=0.07). DOOR outcomes were similar in both groups . Numerically more patients in the ceftriaxone-resistant group on short treatment were in category 3; 4/20 (20%) vs 5/87 (6%) in the long duration group. These 4 patients all had unsuccessful discharge combined with renal failure (n=2), and/or lack of clinical response (n=3).Desirability of outcome ranking (DOOR) analysesShown are the percentages of patients in each group with a specific DOOR category outcome.E. coli BSI. Further studies are needed to determine whether short-course therapy is appropriate for ceftriaxone-R E. coli BSI.Short duration of therapy was less frequently used than long duration of therapy in this prospective cohort of Yohei Doi, MD, PHD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Owen Albin, MD, Charles River Laboratories: Advisor/Consultant|Shionogi: Advisor/Consultant Elie Saade, MD, MPH, FIDSA, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel and Lodging Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBiome: Grant/Research Support Martin Krsak, MD, MSc, FASAM, AbbVie: Grant/Research Support|Melinta: Honoraria W. 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Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant


This paper introduces a new type of gypsum-based humidity-control material. The material combines gypsum–silica gel humidity-control material with 20% sepiolite powder activated by calcium chloride. Both experimental and simulation studies were conducted to assess its humidity-control performance. The experimental results indicate that gypsum-based humidity-control material has the property of absorbing moisture in high-humidity environments and releasing moisture in low-humidity environments. Moreover, both environmental temperature and relative humidity (RH) have an impact on the material’s humidity-control performance. At a relative humidity of 97.4%, the maximum equilibrium moisture content of the material is 0.225 g/g, which is 1.4 times that of the gypsum–silica gel humidity-control material and 4.5 times that of pure gypsum material. The simulation results indicate that gypsum-based humidity-control material effectively mitigates indoor relative humidity fluctuations and maintains indoor air relative humidity within a narrow range. Furthermore, the material has the potential to reduce building energy consumption. This is especially evident under climate conditions with large temperature and relative humidity differences between day and night, such as in Beijing, Paris, and Atlanta. The maximum potential energy-saving rate in Beijing can reach up to 19.31%. The indoor environment plays a crucial role in determining individuals’ physical and mental well-being, a relationship that is primarily affected by indoor environmental parameters ,2,3. RelAs a passive energy-saving technology for regulating indoor humidity, humidity-control materials stand out among numerous passive technologies. The concept of humidity-control materials was initially proposed by Nishito and Miyano in Japan in the 1940s . It refeIn recent years, the utilization of humidity-control materials for regulating indoor relative humidity has yielded promising results ,14,15. ZCurrently, various types of humidity-control materials have been developed and classified as biomass, organic, inorganic, and composite materials . BiomassTo enhance the humidity-control performance of gypsum, numerous researchers have chosen gypsum as the matrix and incorporated other materials to develop gypsum-based composite materials ,27. JianIn conclusion, gypsum is a traditional building material with humidity-control properties, but it has limitations in terms of moisture absorption and desorption performance. The current focus of research lies on composite humidity-control materials ,33, but The study used gypsum material and calcium chloride from Sinopharm Chemical Reagent Co., Ltd., Shanghai, China. Silica gel was obtained from Henan Pubang Environmental Protection Materials Co., Ltd., Henan, China. Sepiolite powder was provided by Aladdin Biochemical Technology Co., Ltd., Shanghai, China. The preparation process of gypsum-based humidity-control material is described as follows.The sepiolite powder was placed in an air-drying oven  to dry at a temperature of 90 °C until the change in weight did not exceed 0.1% over three consecutive days. Subsequently, a 3 mol/L calcium chloride solution was formulated and blended with the dried sepiolite powder at a mass ratio of 8:2 with the aid of an electronic balance . The mixture was subsequently homogenized using a glass rod until it attained a dry and friable consistency to obtain sepiolite power activated by calcium chloride.Firstly, the silica gel was crushed using a crusher  and sieved through a mesh to obtain 3 mm particle-size silica gel. Then, gypsum and silica gel were separately weighed in a mass ratio of 6:4 using an electronic balance . After thoroughly mixing the materials in a beaker, the desired amount of distilled water was added and stirred well. Finally, the well-mixed composite slurry was poured into a precast mold with dimensions of 50 × 50 × 5 mm and allowed to solidify. It was then cured for 24 h at a temperature of 50 ± 2 °C and a relative humidity of 40 ± 5%. This resulted in the formation of the gypsum–silica gel humidity-control material. The detailed preparation procedure can be found in reference .The uncured gypsum–silica gel humidity-control material slurry was mixed with activated sepiolite powder in a mass ratio of 8:2. The mixture was poured into a beaker and the desired amount of distilled water was added, then stirred thoroughly to achieve uniformity. The well-mixed composite slurry was poured into a precast mold with dimensions of 50 × 50 × 5 mm and allowed to solidify. It was then cured for 24 h at a temperature of 50 ± 2 °C and a relative humidity of 40 ± 5%. This resulted in the formation of the gypsum-based humidity-control material.The raw materials used in the sample preparation process, as well as the samples employed during the experimental procedure, are illustrated in The material composition parameters are shown in Humidity-control performanceTo test the humidity-control performance of the gypsum-based humidity-control material, two experimental schemes were designed. First, the gypsum-based humidity-control material was used to dehumidify and humidify high-humidity (85%) and low-humidity (25%) environments consecutively. This continuous humidity-control test was repeated three times. Second, the gypsum-based humidity-control material was used to dehumidify the high-humidity environment (85%) and immediately humidify the low-humidity environment (25%). This intermittent humidity-control test was repeated three times.The experimental setup design schematic diagram illustrated in 2.The impact of the environment on humidity-control performanceTo test the effect of environmental temperature on the humidity-control performance of gypsum-based humidity-control material, the programmable temp&humi chamber  was utilized. A constant relative humidity of 80% and 20%, respectively, was maintained for the experiment. The materials were placed in an air-drying oven to dry at a temperature of 80 °C until the change in weight did not exceed 0.1% over three consecutive days. The dry materials were placed in the chamber with a constant relative humidity of 80% to absorb moisture. In contrast, the materials that had reached the maximum equilibrium moisture absorption at a relative humidity of 97.4% were placed in the chamber with a constant relative humidity of 20% to desorb moisture. The chamber was set to 13 °C, 23 °C, and 33 °C, respectively.To test the effect of environmental relative humidity on the humidity-control performance of gypsum-based humidity-control material, the internal temperature of the programmable temp&humi chamber was kept at 23 °C. The dry materials were placed in the chamber to absorb moisture, and the relative humidity inside the chamber was controlled at a constant level of 50%, 60%, 70%, and 80%, respectively. The materials that had reached the maximum equilibrium moisture absorption at a relative humidity of 97.4% were placed in the chamber to desorb moisture. Inside the chamber, the relative humidity was controlled at constant levels of 20%, 30%, 40%, and 50%, respectively.3.Isothermal moisture adsorption–desorption curveIn accordance with the Chinese standard GB/T 20312-2006 , the iso0 is the dry mass of material (g), m is the mass of the material at moisture equilibrium (g).The equilibrium moisture content u during the process of moisture adsorption and desorption of the above material can be calculated using Formula (1),1 is the moisture content of the material after adsorption or before desorption (g/g), u2 is the moisture content of the material before adsorption or after desorption (g/g).The moisture content U during the process of moisture adsorption and desorption of the above material can be calculated using Formula (2),The actual image showcasing the experimental process of using the programmable temp&humi chamber is illustrated in To test the humidity-control effect of gypsum-based humidity-control material applied in the building, EnergyPlus software (EnergyPlus 9.6.0) was used. The study focused on investigating the impact of material thickness and material laying area on the indoor air parameter changes in a room under summer climate conditions in Xiamen. The simulation period spanned from 1 August to 7 August.To test the energy-saving effect of gypsum-based humidity-control material applied in buildings, EnergyPlus software was used. The study focused on investigating the impact of the laying and non-laying of material on building energy consumption under various climatic conditions. Four cities worldwide characterized by typical urban climates were selected for analysis. These cities include Beijing, China , Paris, France (temperate oceanic climate), Atlanta, United States , and Xiamen, China .For accurate and typical results, the BESTEST base case building shown in  from theThe detailed physical property parameters of each layer in the BESTEST base case building are presented in The simulation settings and boundary conditions are shown in 2 . Case B studied the impact of gypsum-based humidity-control material laying area on its regulating humidity effectiveness. The material laying area was 63.6 m2  and 159.6 m2 , and the material thickness was 0.03 m. Finally, Case C acted as the reference group where no gypsum-based humidity-control material was applied in the room.The results of the continuous dehumidification and humidification tests of the gypsum-based humidity-control material are shown in The results of the intermittent dehumidification and humidification tests of the gypsum-based humidity-control material are shown in To evaluate and compare the humidity-control performance of pure gypsum, gypsum–silica gel humidity-control material, and gypsum-based humidity-control material, an isothermal moisture absorption and desorption test was conducted. The ExpDec1 model in Origin software (Origin 2017) was used to fit the isothermal equilibrium moisture content curve, the formula is as follows,After conducting a simulated study on the impact of different thicknesses of materials laid on the interior of rooms under Xiamen’s summer climate conditions. These results are illustrated in 2, which is significantly better than the energy consumption of 0.01 m and 0.02 m. Compared with laying thicknesses of 0.01 m and 0.02 m, energy efficiency has been improved by 7.25% and 3.17%, respectively. Considering economic factors, we choose 0.03 m as the laying thickness for subsequent simulations.Based on the simulation results, the optimal thickness value of the material cannot be determined solely by changes in indoor air parameters. However, a specific thickness value needs to be determined in subsequent simulations. 2 area, the room with a 159.6 m2 area exhibits a smaller amplitude of moisture content fluctuation.Then, a simulated study was conducted on the impact of different areas of materials laid on the interior of rooms on the indoor air parameters under Xiamen’s summer climate conditions. These results are illustrated in Through the analysis of experimental results, it was found that intermittent dehumidification and humidification have shown more beneficial long-term performance for the material compared to continuous dehumidification and humidification. Moreover, although high temperature can promote the desorption process of gypsum-based humidity-control material, its desorption capacity is still limited under continuously high-humidity conditions. In contrast to temperature, relative humidity has a more significant impact on the material’s humidity-control performance.The simulation results also confirmed the findings. In climates characterized by sustained high temperature and humidity, such as Xiamen, outdoor high temperature increases the accumulated heat load on the material. Additionally, outdoor high humidity hinders the desorption process, resulting in suboptimal discharge of internal moisture. Conversely, in regions with greater fluctuations in temperature and relative humidity throughout the year, such as Beijing, Paris, and Atlanta, the material exhibits excellent energy-saving performance.To better elucidate this finding, Xiamen was taken as an example to categorize the impact of gypsum-based humidity-control material on annual building energy consumption according to the seasons: spring, summer, autumn, and winter. The results are presented in To improve the humidity-control performance of traditional building materials and augment their efficacy in regulating indoor relative humidity, this study incorporated sepiolite powder activated by calcium chloride into gypsum–silica gel humidity-control material to prepare a new type of gypsum-based humidity-control material. Through experimental and simulation studies, the following main conclusions were drawn:(1) Gypsum-based humidity-control material exhibits the ability to absorb moisture in high-humidity environments and desorb moisture in low-humidity environments. However, the material’s humidity-control capacity decreases over time during continuous dehumidification or humidification. Therefore, intermittent dehumidification and humidification are more conducive to maintaining relative humidity stability for extended periods of time.(2) The moisture absorption content of the gypsum-based humidity-control material is minimally influenced by changes in environmental temperatures, while its moisture desorption content is noticeably affected. On the other hand, variations in relative humidity impact both the moisture adsorption and desorption content of the material. The larger the discrepancy between environmental relative humidity and the internal moisture content of the material, the greater the effectiveness of the material’s humidity-control performance.(3) Addition of calcium-chloride-activated sepiolite powder significantly enhances the adsorption and desorption abilities of the gypsum–silica gel humidity-control material. At a relative humidity of 97.4%, the equilibrium moisture content of the gypsum-based humidity-control material can reach a maximum of 0.225 g/g. It is 1.4 times higher than that of gypsum–silica gel material, and 4.5 times than that of pure gypsum materials.(4) Gypsum-based humidity-control material can mitigate the influence of exterior and interior humidity loads on indoor relative humidity. The material can reduce fluctuations in indoor relative humidity and maintain it within a narrow range, providing a more stable indoor environment.(5) Gypsum-based humidity-control material has the potential to reduce building energy consumption. Simulation results show that compared with regions with high temperatures and high humidity throughout the year, this material is more suitable for areas with large diurnal temperature differences and differences in relative humidity.The uniqueness of this study lies in the successful preparation of a novel gypsum-based humidity-control material. It provides a new approach for low-cost and practical humidity-control building materials in the field of architecture. However, there are still several limitations to be considered. This study explores the practical application of gypsum-based humidity-control materials through simulation research methods. Further work requires long-term monitoring and analysis in actual architectural environments to evaluate their actual moisture regulation performance. Additionally, during the preparation process of gypsum-based composite materials, the silica gel and activated sepiolite powder as additives significantly enhance the moisture absorption and desorption properties of the materials. However, considering that silica gel itself belongs to a “strong absorption and weak desorption” material, it leads to relatively poor desorption performance of gypsum-based materials. The next focus of research will concentrate on exploring modification methods to improve the moisture desorption performance of the materials. Simultaneously, it aims to achieve cost reduction objectives and ensure meet energy-saving requirements in continuous high-temperature and high-humidity environments.


This study was performed on a population of 300 graphene field effect transistors. The output characteristic of the transistors revealed that a C60 thin film adsorbate increased the graphene hole density by (1.65 ± 0.36) × 1012 cm−2, whereas a Pentacene thin film increased the graphene electron density by (0.55 ± 0.54) × 1012 cm−2. Hence, C60 induced a graphene Fermi energy downshift of about 100 meV, while Pentacene induced a Fermi energy upshift of about 120 meV. In both cases, the increase in charge carriers was accompanied by a reduced charge mobility, which resulted in a larger graphene sheet resistance of about 3 kΩ at the Dirac point. Interestingly, the contact resistance, which varied in the range 200 Ω–1 kΩ, was not significantly affected by the deposition of the organic molecules.Graphene is an excellent 2D material for vertical organic transistors electrodes due to its weak electrostatic screening and field-tunable work function, in addition to its high conductivity, flexibility and optical transparency. Nevertheless, the interaction between graphene and other carbon-based materials, including small organic molecules, can affect the graphene electrical properties and therefore, the device performances. This work investigates the effects of thermally evaporated C60 ( In fact, the van der Waals interactions of carbon materials, including small organic molecules, e.g., C60-Fullerene and Pentacene, have an important influence on the electrical properties of graphene and therefore, on the device performances. While the growth mechanisms and orientation of C60 and Pentacene molecules on graphene have been widely studied [Hybrid van der Waals heterostructures made of Graphene (Gr) and Organic Semiconductors (OSC) are being widely investigated for their potential applications in sensors ,2, solar studied ,15,16,17n- and p-type organic semiconductors [This work investigates the effect of C60 and Pentacene adsorbates on the electrical properties of large-area graphene grown by Chemical Vapor Deposition (CVD). C60 and Pentacene molecules are commonly used as nductors ,19,20 thW of 5 μm and five different channel lengths L of 5, 10, 20, 50 and 100 μm. The two sets include 30 GFETs per channel length and were fabricated on two separate chips (3). The remaining graphene sheet was transferred on the pre-patterned Ti/Au electrodes (5 nm/50 nm) on a Si/SiO2 (525 μm/300 nm) substrate and patterned into geometrically defined channels by e-beam lithography. Then, the molecules were thermally evaporated, without using any physical mask nor photolithographic patterning, resulting in a uniform coverage of the whole chip. L = 50 μm and W = 5 μm. The output and transfer characteristics of the GFETs were measured in vacuum before and after depositing the molecules, after 24 h of vacuum exposure to assure complete desorption of the moisture and water. 2O and/or resist residues [This study was performed on two sets of 150 Graphene Field Effect Transistors (GFETs) with a fixed channel width te chips . The detresidues ,27,28,292 substrates were about 10 nm and 5 nm, as shown in the 2 and graphene. The AFM profile of 2 and graphene, as was previously reported [2 [2 and on the graphene channel. The presence of the graphene channel under the organic thin films was further confirmed using Raman spectroscopy. 2 substrate) showed the characteristic G (1587 cm−1) and 2D (2681 cm−1) peaks, as well as the D (1340 cm−1) peak [−1) and second-order scattering band (940–980 cm−1) of the Si substrate [1g at 264 cm−1, H2g at 430 cm−1, A1g at 491 cm−1, H3g at 707 cm−1, H4g at 772 cm−1, H5g at 1099 cm−1, H6g at 1242 cm−1, A2g at 1462 cm−1 and H8g at 1568 cm−1, as well as the characteristic Raman peaks of CVD graphene (G at 1587 cm−1 and 2D at 2681 cm−1) observed before the deposition of C60. −1 were assigned to the Ag bands, while the peak at 1595 cm−1 was assigned to the B3g band. The 2D peak (2687 cm−1) of the CVD graphene could be clearly distinguished, whereas the G peak overlapped with the B3g band of Pentacene. The AFM surface morphology combined with Raman chemical analysis confirmed the presence of the geometrically well-defined Gr/C60 and Gr/Pentacene hybrid heterostructures.reported . The avereported . The disreported . Here, treported ). The AForted [2 , whereasorted [2 ,16. Figu−1) peak , with a s the D 10 cm−1 peubstrate , i.e., HDSI vs. GSV) of pristine GFETs and coated GFETs measured under vacuum and at room temperature. The standard deviations are indicated by the shaded areas. Refer to the Experimental Methods section for details on the data filtering and population selection process and to the DSI vs. DSV) and transfer characteristic (DSI vs. GSV) of graphene field effect transistors [GSV range  × 1012 cm−2, against the residual doping of pristine graphene with n0 = (0.20 ± 0.65) × 1012 cm−2 (Chip 1). For the Pentacene molecules, the graphene was electron-doped with an electron density of n0 = (0.55 ± 0.54) × 1012 cm−2, against the residual hole doping of graphene before the deposition with n0 = (0.09 ± 0.48) × 1012 cm−2 (Chip 2). Such a charge transfer could not be anticipated a priori from the HOMO and LUMO energy levels of the individual molecules relative to the graphene Fermi level only, as illustrated for C60 and Pentacene in DSI vs. GSV traces. n0 was accompanied by a decrease, from n0 which was accompanied by a decrease, from GSV range.nsistors . The traGS range , while ang level ,25,26,27acitance ,38, is ge ϵr=3.9  and t=30graphene , i.e., Δurements . The fiety reads ,(2)μ=LgDS=50 mV . The holSR increased by about 200 Ω and shifted to a more positive CR shifted with SR and remained close to the Dirac point, suggesting that the charge carrier injection mechanism at the Au/Gr interface was not significantly affected by the molecules. Assuming that the charge injection mostly occurred at the edge between the metal electrodes and Gr (W = 5 μm), the gate dependent contact resistivity n- and p-type organic semiconductors [ne GFETs a,b showegraphene ,45, weregraphene . On the mobility , assuminon model ,13. Thisnductors ,10,11,1212 cm−2, whereas the deposition of Pentacene results in an increased residual graphene electron density of (0.55 ± 0.54) × 1012 cm−2. In both cases, the increase in the residual charge carriers was accompanied by a reduced charge mobility, possibly due to an increased charge-impurity scattering in graphene. The Fermi energy of graphene shifted to (−150 ± 15) meV after the deposition of C60, and it shifted to (+86 ± 35) meV after the deposition of Pentacene, while the charge carrier injection at the Au/Gr did not seem to be significantly affected. Overall, this work provides useful insight into the graphene in-plane charge transport and on the energetic of the Gr/C60 and Gr/Pentacene hybrid heterostructures, which could be exploited in more complex organic electronic devices. For instance, the energy barriers forming at the Gr/C60 and Gr/Pentacene interfaces and the weak electrostatic screening of graphene could be beneficial for forming n- and p-type channels in graphene-based vertical organic transistors.In summary, CVD graphene field effect transistors (GFETs) with a fixed channel width (5 µm) and different channel lengths  were fabricated and electrically characterized under vacuum. Subsequently, thin films of C60 and Pentacene were deposited on two distinct GFET chips by thermal evaporation and electrically characterized again under vacuum. The GFETs’ transfer characteristic revealed that the deposition of C60 on graphene results in an increased residual graphene hole density of (1.65 ± 0.36) × 102. Then, the foils were placed in Acetic Acid (CH3COOH) for 30 min, rinsed in de-ionized water (DIW) and Ethanol and dried with N2. The cleaned foils were pre-annealed at 1000 °C for 1 h in a H2 (20 sccm) and Ar (200 sccm) atmosphere in the CVD oven (approximately 1 mbar). Then, graphene grew for 35 min in a CH4 (0.05 sccm), H2 (20 sccm) and Ar (200 sccm) atmosphere under a pressure of about 120 mbar. After the CH4 flow was stopped, the CVD oven was left to cool down to room temperature (at approximately 1 mbar).Graphene was grown in-house by chemical vapor deposition (CVD) on copper foils  with a fully automated setup. The foils were ultrasonicated in Acetone, rinsed with Isopropyl Alcohol (IPA) and dried with N2 flow (30 sccm) for 2 min. The Cu substrate was etched away in a Ferric Chloride  bath for 1 h, and then transferred to de-ionized water (DIW). Subsequently, the remaining graphene/PMMA sheet was placed in hydrochloric acid (HCl 10%) for 5 min and transferred back to DIW. Finally, graphene could be transferred onto the target substrate and dried overnight in vacuum oven .The CVD graphene was transferred as previously reported ,46. To p2 (300 nm) substrates. The Au bottom contacts architecture . The remaining PMMA, protecting the graphene channels, was removed in Acetone (55 °C) for 1 h and IPA (55 °C) for 1 h.Two chips including 150 Graphene Field Effect Transistors (GFETs) were fabricated. Graphene sheets grown by CVD on Cu foils were transferred onto photolithography pre-patterned Ti (5 nm)/Au (50 nm) electrodes on Si (525 μm)/SiOitecture b was cho−6 mbar) without further treatments. The C60 thin film was deposited by thermal evaporation at about 0.2 Å/s from a molybdenum evaporation boat (Umicore). The Pentacene thin film was thermally evaporated at about 0.05 Å/s using a low-temperature-controlled source (about 120 °C) with an Al2O3 crucible (Creaphys). The evaporation rate was maintained by monitoring the quartz crystal microbalance of the evaporator. The temperature of the target substrate was not actively controlled during the evaporation.Fullerene-C60  powder was purchased from Sigma-Aldrich , while Pentacene powder  was purchased from Tokyo Chemical Industry . The two types of molecules were thermally evaporated under vacuum (approximately 10−6 mbar) and at room temperature. The samples were shortly exposed to ambient conditions during the transport from the evaporation chamber to the electrical prober vacuum chamber. They were kept in vacuum conditions (approximately 10−6 mbar) for at least 24 h before being characterized. The electronics comprised an AdWin Gold II ADC-DAC unit, a low-noise current-to-voltage converter  to measure the drain-to-source current (DSI), and a high-voltage amplifier  to provide the gate-to-source voltage (GSV). The drain-to-source voltage (DSV) was directly provided by the ADC-DAC. The automated probe station and the ADC-DAC were controlled via LabVIEW and Matlab scripts. In the drain-to-source voltage (DSV) sweep from −50 mV to +50 mV, the voltage step was set to 0.5 mV, the sweep rate to 50 mV/s and the gate-to-source voltage was set to 0 V. In the gate-to-source voltage (GSV) sweep from −50 V to +50 V, the voltage step was set to 0.1 V, the sweep rate to 10 V/s and the drain-to-source voltage (DSV) was set to 50 mV. The internal averaging was set to 20 ms for all the measurements. Only the backward sweep traces were considered for the analysis, refer to the The devices were electrically characterized under vacuum  in tapping mode. The AFM was equipped with a TESPA-V2 cantilever with a tip apex radius of 7 nm, with a resonant frequency of 320 kHz and a spring constant of 37 N/m. The AFM data were processed with Gwyddion (version 2.56) which was used to extract the single and average height profiles and export the images.−1) equipped with a TE-cooled charge-coupled device . One Raman spectrum for each device was collected (150 devices per chip). The laser power was set to 0.1 mW and 0.5 mW for the Gr/C60 and Gr/Pentacene heterostructures, respectively. In both cases, the integration time was set to 30 s. The average Raman spectra of graphene, Gr/C60 and Gr/Pentacene were obtained using all the Raman spectra acquired on each set of devices. Refer to Raman spectra were acquired in ambient conditions using a 532 nm excitation wavelength with a WITec Alpha 300R confocal Raman microscope mounting an 100× objective  and a 300 mm lens-based spectrometer (grating: 600 g mmL. The weights were set to Python scripts were used for the data selection, analysis and visualization. Raman spectra averaging and polynomial background subtraction was done using numpy . The resng scipy . The RC dent TLM .


ImportanceChat Generative Pre-Trained Transformer (ChatGPT) has shown promising performance in various fields, including medicine, business, and law, but its accuracy in specialty-specific medical questions, particularly in ophthalmology, is still uncertain.PurposeThis study evaluates the performance of two ChatGPT models (GPT-3.5 and GPT-4) and human professionals in answering ophthalmology questions from the StatPearls question bank, assessing their outcomes, and providing insights into the integration of artificial intelligence (AI) technology in ophthalmology.MethodsChatGPT's performance was evaluated using 467 ophthalmology questions from the StatPearls question bank. These questions were stratified into 11 subcategories, four difficulty levels, and three generalized anatomical categories. The answer accuracy of GPT-3.5, GPT-4, and human participants was assessed. Statistical analysis was conducted via the Kolmogorov-Smirnov test for normality, one-way analysis of variance (ANOVA) for the statistical significance of GPT-3 versus GPT-4 versus human performance, and repeated unpaired two-sample t-tests to compare the means of two groups.ResultsGPT-4 outperformed both GPT-3.5 and human professionals on ophthalmology StatPearls questions, except in the "Lens and Cataract" category. The performance differences were statistically significant overall, with GPT-4 achieving higher accuracy (73.2%) compared to GPT-3.5  and humans . There were variations in performance across difficulty levels (rated one to four), but GPT-4 consistently performed better than both GPT-3.5 and humans on level-two, -three, and -four questions. On questions of level-four difficulty, human performance significantly exceeded that of GPT-3.5 (p = 0.008).ConclusionThe study's findings demonstrate GPT-4's significant performance improvements over GPT-3.5 and human professionals on StatPearls ophthalmology questions. Our results highlight the potential of advanced conversational AI systems to be utilized as important tools in the education and practice of medicine. Chat Generative Pre-Trained Transformer (ChatGPT) is a natural language processing model that was developed by OpenAI and released in November 2022 . It has In the field of ophthalmology, artificial intelligence (AI) models like ChatGPT can play a crucial role in answering patient-specific management questions, providing quick insights on relevant criteria, and facilitating discussions on ocular conditions, treatments, and procedures. However, despite its success in the overall fields of medicine, business, and law, ChatGPT has been shown to have variable accuracy in answering specialty-specific medical questions ,6.OpenAI has developed two prominent iterations of the ChatGPT model, namely GPT-3.5 and GPT-4. The latest version, GPT-4, boasts improved efficiency and accuracy compared to its predecessor. Notable advancements include enhanced contextual understanding, improved language fluency, and an expanded knowledge base . HoweverThis study aims to evaluate the performance of GPT-4, GPT-3.5, and human professionals in answering ophthalmology questions sourced from the StatPearls question bank, a resource that provides practice questions commonly used by residents, fellows, and attendings to prepare for board exams and clinical practice . The prihttps://www.ncbi.nlm.nih.gov/books/NBK430685/). “Ophthalmology” was used as a search criterion to filter relevant StatPearls questions. The search yielded 548 entries or 1,096 questions. The results were sorted in alphabetical order and a random number generator was used to select each entry. The question was omitted if it was not directly relevant to ophthalmology. The questions were then pasted into ChatGPT, preceded by the statement, “Please choose the best answer and explain your reasoning:”ChatGPT's performance was evaluated utilizing StatPearls ophthalmology questions, which are peer-reviewed questions from a medical question bank designed to be at the level of ophthalmology residents, fellows, and attendings. Free StatPearls questions were accessed via the National Library of Medicine bookshelf  Exam Content Outline was referenced when creating ophthalmology subcategories in which to organize the questions . The queChatGPT responses were organized by GPT model, question difficulty on a scale of 1 to 4, ophthalmology subcategory, and generalized anatomical category. Performance of GPT-3.5, GPT-4, and humans in answering ophthalmology practice questions was measured as the proportion of correct answers. Our secondary outcomes were the proportion of questions GPT-3.5, GPT-4, and humans were able to answer correctly within different difficulty levels.The study demonstrated a power of 0.80. Each of the three groups underwent a set of 467 questions, resulting in a sample size of 1,401. The effect size of 0.083, calculated using the G*Power software , was employed as a parameter in the analysis.Statistical analysis was performed utilizing Microsoft Excel  and SPSS Statistics Software . The Kolmogorov-Smirnov test was used to test for normality. Due to the normal distribution of the data, a one-way analysis of variance (ANOVA) was used to test for the statistical significance of GPT-3 versus GPT-4 versus human performance. To compare the means of the two groups, repeated unpaired two-sample t-tests were used. P-values were 2-tailed where applicable, and a p-value of less than 0.05 was considered statistically significant.GPT-4 performed significantly better than both GPT-3.5  and humans  on 467 ophthalmology StatPearls questions. When comparing individual categories, GPT-4 performed superior to both GPT-3.5 and humans in all categories except “lens and cataract”, in which humans performed better . However, this was not a statistically significant difference, likely due to the small sample size of level-one questions (n = 7). GPT-3.5 and human professionals performed similarly on level two and three questions while humans significantly outperformed GPT-3.5 on level-four questions . GPT-4 performed superior to both GPT-3.5 and humans on level two, three, and four questions (p < 0.001). Despite the variability in performance exhibited by GPT-3.5 and GPT-4 across difficulty levels, human performance remained relatively consistent. Acknowledging that GPT is incapable of directly analyzing images referenced within questions, the inclusion of images in the question stem did not yield any statistically significant differences in the performance of GPT-3.5 and GPT-4.Advancements in artificial intelligence have had profound impacts on many industries, including healthcare. One significant application of AI in healthcare is the development of conversational AI models, such as ChatGPT, which have the potential to assist medical professionals in providing accurate and timely information.Recent studies have focused on examining ChatGPT's roles in clinical decision-making, generating differential diagnoses, and providing insights into treatment options -12. In aWhen evaluating the performance of the models in individual subspecialty categories, GPT-4 demonstrated superiority over both GPT-3.5 and humans in all categories except for the "lens and cataract" category. While this category did not contain an increased number of higher-order questions compared to the other categories, it is possible it may have posed specific challenges that affected the performance of GPT-4. Such difficulties could stem from the presence of specific enhancements in the field of lens and cataract that may not be updated or reflected in ChatGPT’s training. Alternatively, it is conceivable that ophthalmology residents and fellows are more familiar with cataracts and lens-related topics, as they constitute the fundamentals of clinical practice. Further investigation into the specific difficulties encountered within this category could provide valuable insights for future model enhancements.The differences in performance between the models and humans varied across difficulty levels Figure . When thThe findings of this study have significant implications for the field of ophthalmology and the development of conversational AI systems. The superior performance of GPT-4 over both GPT-3.5 and humans suggests substantial rapid advancements in AI-based question-answering systems. GPT-4, released in March 2023, was able to achieve or surpass human performance within four months of its predecessor's release in November 2022. Earlier studies have highlighted the performance distinction between GPT-4 and GPT-3.5 on the OKAP exam with inferior accuracy of GPT-3.5 ,17. SimiThese improvements may enhance the accessibility and accuracy of medical information for healthcare professionals and patients alike, thereby potentially improving patient care and outcomes. However, it is important to note that GPT-4 is currently less accessible than GPT-3.5. Members must pay a monthly fee to use GPT-4 and are limited to 25 messages over the course of three hours. Additionally, both GPT-3.5 and GPT-4 have a knowledge cutoff of September 2021, which may limit the accuracy of these models in providing responses within a field that is constantly evolving. At present, these factors may be considered a barrier to the use of ChatGPT in clinical practice and education, as GPT-3.5 was shown to have inferior reliability in answering questions of varying difficulty and ophthalmic content.The current study has some limitations. First, it cannot be conclusively stated that these questions are only answered by ophthalmology residents, fellows, and attendings, though there are many factors that contribute to the answering pool consisting of only these groups such as a financial subscription and inputting proper credentials into the StatPearls portal for the respective question banks. Second, the evaluation was focused solely on ophthalmology StatPearls questions, which may not fully capture the range of complexities encountered in clinical practice. Although StatPearls has the credibility for the education of residents and fellows in various medical specialties, better standardization may be necessary to differentiate clinical judgment from mere factual knowledge. It cannot be conclusively stated that StatPearls multiple-choice questions are a gold standard for demonstrating enhanced cognitive understanding of medical thought processes by AI. Further studies should include a broader set of specialty-specific medical questions to assess the generalizability of the observed performance differences. Additionally, the human participants in this study may not represent the entire population of healthcare professionals, and their performance may be influenced by individual variations in expertise and experience.The results of this study demonstrate the significant improvements in performance achieved by GPT-4 compared to GPT-3.5 and human professionals on ophthalmology questions sourced from a professional-level question bank. While GPT-4 outperformed both GPT-3.5 and humans in most categories and difficulty levels, the “lens and cataract” category presented a unique challenge for the model. These findings highlight the potential of advanced conversational AI systems in the medical domain and emphasize the need for further research and development to address specific challenges encountered in different medical specialties.We support the use of AI as an adjunct in education and medicine rather than a replacement for human professionals. The results of this study indicate the advanced ability of AI models to answer multiple-choice questions, but the model’s performance on these questions is not a direct indicator of clinical aptitude. While the rapid advancement of GPT-4’s ophthalmic question-answering ability may foreshadow an increasing incorporation of the AI model into medical practice, an emphasis should be placed on using AI systems both responsibly and cautiously.


Microbiology wet labs have been eliminated in many medical schools and infectious diseases (ID) fellows are training in a post-COVID era where hands-on experience is lacking. The IDSA recommends 120 hours of microbiology experience for fellows, but feasibility is limited in centers struggling to retain adequate staff, and technicians are limited in their ability to integrate clinical skills. We aimed to overcome these struggles by implementing a microbiology and mycology curriculum for ID fellows using a case-based approach within the microbiology lab .In a quasi-experimental study, eight ID fellows from Wayne State University were taught in interactive, 1-hour sessions delivered monthly in the lab over 11 months using existing samples. Planning included a needs assessment, review of in training scores to identify weak spots, and pre-tests to assess baseline knowledge . Sessions topics are shown in Table 1. All sessions were delivered by an ID faculty to ensure homogeneity. Prior to each session, specimens were procured and objectives were outlined and linked to core content areas. An example of the objectives and core content for the hyaline mold session is shown in Table 2. A post-test occurred after session 9. Primary outcome was comparison of de-identified pre and post test scores by Wilcoxon signed-rank test for paired non-parametric data. Fellows experience and feedback for improvement were also collected.Sessions were performed as described and included hands on activities and a summary handout . Pre versus post test scores showed significant median improvement . Feedback on the sessions was overwhelmingly positive, with suggestions for encore sessions and request to make a similar parasitology curriculum (Table 4). Sessions became so popular that pharmacists and other trainees began attending. Although not an intended outcome, it was noted that after posting handouts to twitter, fellowship following increased by 250%.A monthly longitudinal microbiology and mycology curriculum was well received by ID fellows and objectively increased their knowledge. This is the first study attempting to objectively quantify knowledge gained using a hands-on microbiology lab curriculum to teach ID fellows.All Authors: No reported disclosures


Respiratory monitoring is crucial for evaluating health status and identifying potential respiratory diseases such as respiratory failure, bronchitis, and pneumonia. Humidity sensors play a significant role in this regard, and efforts are being made to improve their performance. However, achieving ideal sensor parameters such as sensitivity, detection range, and response speed is challenging. In this work, we propose a flexible preparation method for a double-layer humidity sensor using PDMS as a substrate and a GNP/MWCNT composite material as a sensor element. This sensor exhibits high sensitivity (1.4 RH-1), a wide detection range (20–90%), ultra-fast response (0.35 s) and recovery (2.5 s), high repetitiveness (500 cycles), good long-term stability, and excellent flexibility. Due to these advantages, this sensor has potential applications in real-time clinical and home medical care, such as accurate human respiratory monitoring and non-invasive skin humidity monitoring. Hence, this humidity sensor can be a powerful tool to monitor respiratory moisture levels for diagnosing and treating respiratory diseases effectively. The monitoring of human respiration is crucial for the early detection of diseases and the management of personal health . HoweverIn recent years, the development of flexible electronic technology has introduced new possibilities for respiratory monitoring . As an iHumidity sensors available on the market have certain limitations with regards to their sensitivity, response, and detection range. For instance, Ghanem et al.  used a sCompared with traditional preparation methods ,27,28, t2O, concentration: 1 mg/mL); Multi-wall carbon nanotubes (MWCNT) ; Polyethylene oxide (PEO) (average molecular weight: 3 million); Polydimethylsiloxane (PDMS) ; Electrode material HS-8200 Ag .The following were used in this study: Graphene nanoflakes (GNPs), dispersed solution  into rectangular bases of length × width = 1.5 cm × 1 cm using a blade. Activate the surface of the rectangular base using plasma  for 3 min to increase the surface energy of the PDMS base and to enhance the adhesion between the electrode-sensitive unit and the surface of the PDMS substrate.Z-axis motion platform, a heating-plate module, and an industrial CCD camera module. The direct-writing inkjet module is composed of a syringe pump  and a direct-writing nozzle. When the printing begins, the Z-axis motion platform is adjusted to bring the direct-writing nozzle to a distance of ~1 mm from the surface of the PDMS substrate. By setting a certain liquid discharge rate to the syringe pump, the direct-writing nozzle begins to emit liquid due to the extrusion pressure of the syringe pump. The high-precision motion platform is controlled by a computer to move according to the pattern. The heating-plate module on the Oxy motion platform is used for rapid solidification of the direct-writing pattern, and the heating temperature is set to 80 °C. The industrial CCD camera is used to observe the liquid emission and pattern formation of the direct-writing nozzle.A self-made 3D printing system is used to fabricate humidity-sensitive sensor units, which mainly consists of a direct-writing inkjet module, a high-precision Oxy motion platform (with a minimum movement resolution of up to 0.001 μm and a movement accuracy of ± 0.2 µm), a Morphology characterization: The macroscopic appearance of the sensitive unit is observed using optical microscopy ; the contact angle of water droplets on the surface of the PDMS substrate is measured using a contact-angle measuring instrument ; the microstructure of the sensitive unit is observed using scanning electron microscopy ; the internal microstructure of the sensitive unit is examined using transmission electron microscopy ; the structure of the wet-sensitive GNP/MWCNT unit is analyzed using an X-ray diffractometer (XRD) .Electrical- and humidity-sensing characteristics testing: A gas control system  is used to control the entry of dry N2 or humid N2 into the chamber to regulate the humidity. The calibration of chamber humidity is performed using a precision humidity meter . The flexible humidity sensor is placed in the chamber for testing, and data are collected and recorded using a multifunctional digital multimeter  and a computer.The sensitive unit structure of the flexible humidity sensor is manufactured using a self-made direct-writing printing system a. When tA flexible humidity sensor with a linear structure was manufactured by direct-writing printing a. The thAs shown in When using flexible devices in bending and stretching, the wet-sensitive material at the interface is prone to detachment from the substrate, leading to increased electrical resistance, drift, or even failure at the baseline of the device. Therefore, stable bonding between the sensitive unit and the flexible substrate is crucial to ensure the stability, accuracy, and reliability of the sensor performance. During the direct-writing printing process, the adhesion of the wet-sensitive unit on the PDMS substrate surface is poor. It is difficult to deposit the wet-sensitive unit stably on the surface of PDMS, and it is prone to detachment a. With tTo enhance the adhesion of the PDMS substrate, plasma oxidation activation was employed to treat the PDMS surface. In rh was calculated according to formula (1).The linear flexible humidity sensor was placed in the self-built humidity detection system . The cha∆R refers to the change in resistance value; R refers to the initial resistance value without pressure applied, and δRH refers to the resistance value with pressure applied.−1. As the relative humidity increases from 20% to 90%, ∆R/R increases from 0 to ~0.98, indicating that the change in relative humidity has a significant impact on the resistance of the sensor. That is, the resistance of the sensor gradually increases with the increase of humidity, which is consistent with the analysis of the humidity-sensitive mechanism.As shown in Relative humidity was tested in increments of 10%RH, and 500 repeated tests were conducted as shown in By rapidly opening and closing the valve, drying N2 or N2 with moisture can be quickly introduced. −1, the ∆R/R value increased from 0 to ~0.005. The bending deformation of the sensor almost does not have a significant impact on its resistance, indicating that the flexible humidity sensor is suitable for use in bent environments. Moreover, this characteristic makes the sensor’s accurate in surface adhering testing. As shown in To evaluate the interference of bending deformation on the performance of the flexible humidity sensor, the response characteristics of the sensor’s bending deformation were tested at different curvatures. The linear flexible humidity sensor was attached to the surface of stepped shafts with different radii of 18 mm, 9 mm, 6 mm, 4.5 mm, and 3 mm a. As theThe humidity-sensitive mechanism model is shown in It is well known that the human respiratory process involves periodically inhaling relatively dry air and exhaling relatively humid air, which can cause significant changes in the humidity around the nose or mouth. Flexible humidity sensors with a rapid response can play an important role, especially in respiratory monitoring. This type of sensor can measure the humidity in exhaled air to determine the breathing rate. The normal respiratory rate of adults ranges from 12 to 20 times/min, which is about 3 to 5 s per breath. Breathing rates that are too fast or too slow can have adverse effects on human health. A fast breathing rate can cause shallow breathing and hypoxia, affecting the heart rate and circulation, causing anxiety and tension, and worsening respiratory diseases such as asthma. A slow breathing rate can cause carbon dioxide retention and acidosis, affecting the nervous system and cognitive ability and causing issues such as dizziness and fainting. Therefore, using flexible humidity sensors for real-time monitoring of breathing rates is essential for maintaining good health.As shown in The response of the sensor under normal breathing and breath-holding conditions was evaluated. As shown in As human skin can generate and distribute moisture, the sensor will respond promptly to changes in the surrounding humidity when the finger is close to the sensor. In this work, we have successfully demonstrated a flexible humidity sensor using direct-ink-printed GNPs/MWCNTs as the sensing electrode material and PDMS as the flexible substrate. The device features an ultra-fast response (0.35 s)/recovery (2.5 s), high sensitivity (1.4 RH-1), and high repeatability (500 cycles). Benefiting from these advantages, the device has been evaluated in monitoring human breathing patterns, such as rapid breathing, normal breathing, deep breathing, breathing and breath-holding, nose breathing, and mouth breathing. Additionally, we have verified the prospects of using this humidity sensor in non-contact detection. We believe that in the future, this sensor can be used to accurately sense abnormal human breathing behaviors, including suffocation, respiratory arrest, and asthma, thus playing an important role in human health monitoring.


Sarcoidosis affects approximately 1% of the population. There are two situations where it came become life threatening: seizures secondary to neuro-sarcoidosis and arrhythmias due to cardiac infiltration. Currently there are limited licenced therapies for the treatment of sarcoidosis. We describe a case of cutaneous and neuro-sarcoidosis who developed subsequent multi-system sarcoidosis.A previously fit and well 50-year-old presented to his local hospital with tonic clonic seizures. He worked as a mortgage broker and never smoked. There was no pro-drome and on examination it was noted he had erythema nodosum on his shins. He was investigated with a CT head and subsequent MRI demonstrating enhancement of his leptomeninges, mid brain parenchyma, hypothalamus and pituitary gland. A lumbar puncture was performed with an elevated protein level of 934g with a normal glucose and lymphocyte level. The CSF was negative for TB. A CT of his chest was performed demonstrating bilateral hilar lymphadenopathy and subsequent histology of these lymph nodes demonstrated non-necrotising, non-caseating epithelioid granulomas. A diagnosis of sarcoidosis was made and he was commenced on mycophenolate. His disease remained quiescent for 5 years before the eruption of further skin lesions. He developed multiple subdermal nodules on his fingers, wrists, elbows which were biopsied demonstrating cutaneous sarcoidosis. Neurological examination demonstrated brisk lower limb reflexes with upgoing plantars. He was commenced on a tapering course of prednisolone and an evaluation for extra-cutaneous disease was made. An IL2Ra was 4719ng/L (423-1843) with a normal ACE. Pituitary axis testing revealed a slightly raised prolactin (326 mIU/L). A CT-PET was performed demonstrating extensive metabolic activity in his skin, central nervous system, liver, spleen, salivary glands, skeletal uptake in both humeral heads alongside myocardial uptake. An urgent cardiac MRI was performed demonstrating active myocardial disease. An ECG did not demonstrate any conduction abnormalities. A diagnosis of multi-system sarcoidosis was made warranting an urgent MDT discussion given the progression of his disease.In this particular case, it had been assumed that his sarcoidosis was inactive until the emergence of the skin lesions. It was the skin lesions that lead to an assessment for multi-system sarcoidosis. It is common for the serum ACE level to be normal, as seen in up to 50% of cases and it was the Il2Ra elevation that prompted the CT-PET request. Given the extent and progression of disease despite treatment with mycophenolate, this gentlemen was given a tapering regime of prednisolone (starting at 20mg) and his mycophenolate was switched to methotrexate which has shown to have superior efficacy to mycophenolate for sarcoidosis. Furthermore, infliximab at a dose of 5mg/kg was commenced shortly after to control the increasing CNS lesions. Infliximab is a well recognised treatment for sarcoidosis; however, due to limited clinical trial data, it remains unlicenced for use in sarcoidosis with the exception of neuro-sarcoidosis (following the failure of DMARD therapy). To date, the patient remains well with no further worsening in his disease.Sarcoidosis is a clinical entity with no one specific test. The diagnosis should be constructed using multiple parameters including radiographic findings, biochemical and histological proof. We advocate that suspected cases of sarcoidosis should have a thorough assessment and discussion in the MDT. When isolated skin disease is suspected or confirmed, baseline testing for extra-cutaneous involvement should be sent including NT-proBNP, troponin I and T, creatinine kinase, a full pituitary profile, ACE and cytokine assessment for Il2Ra, amongst other routine blood tests. An ECG is of paramount importance as arrhythmias are common cardiac features of sarcoidosis. Should there be ongoing suspicion of multiple organ involvement, a CT-PET should be performed at baseline. Isolated lymph node disease does not commonly warrant treatment; however, this cohort of patients should be closely monitored. The management of sarcoidosis in the acute setting is commonly prednisolone, but steroid sparing therapies should be considered in patients needing recurrent, prolonged courses of corticosteroids or those with evidence of critical organ involvement such as CNS, cardiac or lung disease. Life threatening disease or disease refractory to DMARD therapy should be considered for anti-TNF therapy with infliximab or adalimumab. More recently, tofacitinib has been promising as a treatment for sarcoidosis with clinical trials in Yale and Portland. Newer therapies in development include the GM-CSF inhibitor namilumab, and efzofitimod, a neuropilin 2 inhibitor.


K points that is qualitatively consistentwith moiré models of the Hartree–Fock interaction. Weprovide evidence of correlation-enhanced inversion symmetry-breaking,manifested by gaps at the Dirac points that are tunable with doping.These results suggest that electronic interactions play a significantrole in the physics of tBG even at intermediate twist angles and presenta new pathway toward engineering band structure and symmetry-breakingphases in moiré heterostructures.Near the magic angle,strong correlations drive many intriguingphases in twisted bilayer graphene (tBG) including unconventionalsuperconductivity and chern insulation. Whether correlations can tunesymmetry breaking phases in tBG at intermediate (≳ 2°)twist angles remains an open fundamental question. Here, using ARPES,we study the effects of many-body interactions and displacement fieldon the band structure of tBG devices at an intermediate (3°)twist angle. We observe a layer- and doping-dependent renormalizationof bands at the  U to bandwidth W in a system becomes large (U/W ≫ 1), presenting instabilities to myriad groundstates. Twisted bilayer graphene is an especially popular host ofcorrelated phases3 due to the ability to tune the bandwidth with extremeprecision using the twist angle,5 and the ability to tunethe interaction strength U in situ through chargecarrier6 and substrate-based7 screening.The searchfor intriguing phasesof matter often treads along common avenues: generating strong correlationsand breaking symmetries in materials. Correlations develop when theratio of interaction strength 11 and Hartree–Fock interaction,12 which have been shown in some cases to drive correlatedphases outside the twist angle regime predicted by early band structuremodels.13 However, graphenedevices are rarely inversion symmetric,14 especially in the presence of a displacement field, and at twistangles θ ≳ 2° the K point electronicstructure is layer polarized,15 in principleenabling each layer to host differing electronic properties or phases.When inversion symmetry is broken, so far it is unclear how introducingcorrelations affect electronic structure in each individual layerof twisted graphene and whether these differences could independentlytune symmetry breaking phases in each layer. Here, we use gated ARPES18 to directly measure the layer-dependent electronic structure ofan intermediate angle (3°) twisted bilayer graphene device asa function of electrostatic doping and displacement field. The highmomentum and energy resolution of our experiment allow us to identifydirect evidence for layer-dependent interaction-driven band narrowingas well as a substrate-induced band gap at the K points.We find that a combination of displacement field and electron–electroninteractions is able to enhance this band gap within just a singlelayer and thus tune the level of symmetry breaking in the system withatomic layer precision.Most studies of renormalizationeffects in twisted bilayer grapheneto date have focused on how the overall bandwidth is modified by interactions.Indeed, several theoretical works predict significant band structuremodification from the Hartree20 we produce a scanning photoemission micrograph(SPEM) (panel d) that maps the real space configuration of the graphenephotoelectrons at EF and confirms thesample geometry. The intensity of the signal deriving from graphenescales with the layer number:19 the middleregion has a stronger intensity than the region on the left, matchingthe expected location of the tBLG and monolayer graphene regions,respectively as outlined in panel b.K points of thetwo graphene layers are circular Fermi contours whose matrix elementssmoothly drop to zero along one side, suggesting that the low energyFermions in the sample are of Dirac nature.22 Upper and lower graphene layers can be distinguished by the differencein spectral weight near the respective K points,as the photoelectrons from the bottom layer are attenuated as theypass through the top layer.25 The twist angle can be measuredin ARPES from the momentum separation of the K pointsof the two graphene layers using the relationship ΔK = 2 |K| sin θ/2. On the sample a twist angleof 3° was measured, corresponding to a moiré wavelengthof 6 nm and a momentum separation ΔK ≈0.09 Å–1. The angular alignmentof the hBN substrate can be extracted in a similar manner: the momentumseparation of ≈0.54 Å–1 between the ky locationof the hBN K point (parabola at EF – 2.2 eV in panel f) and the lower graphene K point indicates a ≈19° relative twist.Kupper – Klower direction. At large (>2°) twistangles,the K point spectra for the upper and lower graphenelayers can be approximated as Dirac cones.26 This is apparent visually by eye within≈200 meV of the Fermi level in panel f, whose bands from leftto right we label as a, c, f, and h. Around 200 meV below EF (panel f), a van Hove singularity forms fromthe hybridization between intersecting bands from the lower and uppercones.25 Other evidence of graphene–graphene interlayercoupling in our sample is very prominent: Dirac cone replicas of theupper and lower layers are clearly observed at the corresponding miniBrillouin zone (mBz) corners (panel e), and at energies beyond 500meV (panel f) a series of additional bands  are present,similar to previous reports on SiC-supported graphene samples at similartwist angles.27EF. Due to the imperfect out-of planescreening in graphene multilayers, application of a back gate voltage Vbg to our sample generates an electric fieldbetween the upper and lower graphene layers, resulting in both a differencein charge carrier density δ n = nu – nl and chemicalpotential difference D = μu – μl29 (see Upon applying a negative(positive) back gate voltage to the sample,the two graphene layers become doped by holes (electrons), resultingin an upward (downward) shift of the Dirac cone spectrum with respectto μl29 see 2a.29Such an effect, illustrated bythe cartoon in n = kF2/π for the upper and lower Dirac cones,is quantified in Supplementary Note 1 for details).Away fromthe neutrality point at Vg = 1 V, thedensity scales linearly with gate voltage, i.e., n(Vg) ∼ C Vg, implying that the system is effectively a parallel platecapacitor with geometric capacitance C. Near theneutrality point, n(Vg) flattens, suggesting contributions of quantum capacitance due toa strong drop in the density of states, likely from the presence ofa gap in the dispersion (see Supplementary Note 6 for more details). We will return to this point later inthe text.The carrier density, calculated as a = 0.09 ± 0.01 and a = 0.06 ± 0.01 forlower and upper layers, respectively). The band displacement, takenas the difference between the two Dirac cone energies, therefore hasthe same qualitative scaling b = 0.03±0.01.Linear fits to the band dispersions (dashed linesin panel c) atlow energy yield the position of the Dirac point for the upper andlower layers, which are plotted as a function of gate voltage in panele. The Dirac point position as a function of voltage roughly scaleas EF – ED and n(Vg) with gate voltage in the lower layer indicatesthe largeramount of charge induced by the gate in the lower layer, confirmingprevious reports on large twist angle bilayer graphene.29The stronger scalings of both As we shall demonstratein the following, both doping and displacementfields can be used to control the band structure beyond what wouldbe expected by a single particle picture.K point electronicstructures as a function of doping for the 3° twisted graphenesample. Klower for dopings of −2.0 × 1012 cm–2, −0.1 × 1012 cm–2, and1.0 × 1012 cm–2 . These dispersions have been shifted by theposition of the Dirac point of the upper layer for the ease of comparison.From the raw data, it is clear by eye that all three spectra are linearwithin 300 meV of the Dirac point. Notably, the hole-doped dispersion(green) is less steep than the dispersion at neutrality (brown), whichis less steep than the dispersion at electron doping (red). Indeed,a similar effect occurs in the upper layer .Further investigation is necessary to determine the exact origin ofthis behavior.These results clearly indicate a narrowing of the valence bandupon hole-doping and are summarized in panel c, where the band velocities,measured by the slope of the dispersion, are plotted as a functionof doping. These results do not match the behavior of monolayer graphene,educed vF−35 and cCx2 inversion symmetry breaking in the graphene sample. While this oftenoccurs in graphene samples supported by hBN substrates42 or undergoing heterostrain,43 the levelof symmetry breaking here is doping dependent. This signature is inother parts of the electronic structure.The difference in band velocity in the upperand lower layers isclear evidence of K point electronicstructure with doping and a displacement field. Charge neutral ARPESspectra at the upper layer K point (1) exhibit thetypical Dirac cone dispersion with a crossing at the Fermi level.Given a sample temperature of 300 K, division by the Fermi Dirac distributionprovides insight into the electronic structure within 4kBT ≈ 100 meVof the Fermi level , which presents a drop in the densityof states at the neutrality point followed by the bottom of a conductionband which is energetically separated from the valence band by ≈130meV. This can be confirmed by the raw MDCs spectra (panel b1) which are dispersionless in a similar range in energy. Similarelectronic structure is observed in the lower layer K point electronic structure These data constitute direct evidence for a band gap in this twistedgraphene/hBN sample near the charge neutrality point. Such propertyis observed in samples with broken Cz2 inversion symmetry, which can occur in the presenceof an hBN substrate.44 K point 4a1 exhib2, b2) appears similar to the spectrumat neutrality but rigidly shifted by about 150 meV, with the bandgap remaining relatively constant. However, the lower layer band structure undergoes significant modification:whereas the spectrum at neutrality has one valence band, the electrondoped spectrum (panel d2) exhibits two. Indeed, the rawMDCs spectra (panel e2) exhibit 2 peaks, represented asshoulders, between 500 and 200 meV below EF. Interestingly, these peaks at higher momenta have dispersion andenergy very similar to those of the valence band of the upper Diraccone (red curves in panel a2 and red peaks in panel b2). We therefore propose the lower energy band (red dashedlines in panel d2) to be a replica of the upper layer electronicstructure and to be independent of the lower layer electronic structure.Indeed, such replicas manifest in zone-unfolded band structure calculationsin the presence of an electric field between upper and lower graphenelayers (see Supplementary Note 3 for moredetails). The lower layer valence band at higher energy (white dashedline in panel d2) is therefore dramatically separated fromthe conduction band, indicating a significant increase in the bandgap size with doping and displacement.Upon electron doping the sample, the upper layerelectronic structure. The magnitudeof the band gap is determined from the energetic distance betweenlinearly dispersive regions in the band structure which are denotedby dashed black lines. Upon application of a 61 meV displacement anddoping the upper layer by 0.3 × 1012 cm–2, the bandgap at Kupper remains constantat 140 ± 50 meV. However, upon applying the same band displacementand doping the lower layer by 1.0 × 1012 cm–2 the bandgap at Klower increases from130 ± 50 meV to 200 ± 50 meV. Such layer-dependent dopingbehavior of band gaps in our data, summarized in panel h, are qualitativelyconsistent with the amount of inversion symmetry-breaking presentin the sample.The layer and dopingdependent behavior of the band gaps is confirmedby the quasiparticle dispersions in the upper and lower K points, . The magnitudeof the band gap is determined from the energetic distance betweenlinearly dispersive regions in the band structure, which are denotedby dashed black lines. Upon application of a 61 meV displacement anddoping the upper layer by 0.3 × 1012 cm–2, the bandgap at Kupper remains constantat 140 ± 50 meV. However, upon applying the same band displacementand doping the lower layer by 1.0 × 1012 cm–2 the bandgap at Klower increases from130 ± 50 meV to 200 ± 50 meV. Such layer-dependent dopingbehavior of band gaps in our data, summarized in panel h, are qualitativelyconsistent with the amount of inversion symmetry-breaking presentin the sample. Indeed, the inversion symmetry-breaking produced bya misaligned hBN substrate44 can be significantlyenhanced by electron–electron interactions.47 In graphene, the magnitude of interaction-drivengap enhancement scales with the interaction strength,47 which in tBG scales linearlywith doping.11 Therefore, a charge imbalance between the two graphene layers, generated,e.g., via a displacement field, can drive a doping-dependent gap mechanismwhich enables layer-dependent gap enhancements such as those seenin our experiment.The layer and doping dependent behavior of theband gaps is confirmedby the quasiparticle dispersions in the upper and lower 50 Whereas other probes such as transport and STS commonly define gapsas regions with zero density of states, ARPES defines the band gapusing the band edges, at which the density of states rarely has anabrupt drop to zero.42 Impurities may alsocontribute to in-gap states that decrease the apparent gap size ina transport or STS measurement. Notably, both single layer51 and bilayer graphene52 in particular exhibit in-gap conductive resonances as a responseto the presence of charged impurities, which significantly altersthe accuracy of a gap measurement using STS dI/dV or transport. ARPES can still measure the gap in thesecases because band edges are bordered by regions of dispersionlessspectral weight.45 Finally, as transportis only sensitive to the spatially integrated electronic states atthe Fermi level, it may miss the gap entirely because (1) at the neutralitypoint, the spatially inhomogeneuos doping present in tBG samples54 can produce insulating regionsadjacent to conductive regions, which upon spatial integration couldappear as a minor decrease in conductivity50 (see Supplementary Note 5 for more details),and (2) upon electron doping, the gap increase observed here occurswhen the Dirac point is below the Fermi level.The magnitude of gaps observed in our datais much larger thanthose observed in the literature at similar twist angle.Supplementary Note 7), we believe that theseeffects can be best explained by a combination of the substrate interactionand the spatially inhomogeneous Hartree–Fock interaction, whichis controlled within different layers by using a displacement field.Indeed, these interactions can qualitatively explain the presenceof the gap at charge neutrality, the linear dependence of band velocitywith doping and the layer-dependent gap enhancement upon electrondoping the sample.The data reportedhere provide evidence for a method of tuningthe band velocities and band gaps in twisted bilayer graphene in operando.While we considered several alternative explanations (see 56 and other heterostructures.60In conclusion, we have demonstrated thatgated ARPES is an exceptionaltool to study the interplay of interactions and symmetry breakingin 2D homo- and heterostructures. Our results indicate that both thespatially inhomogeneous Hartree interaction and a displacement fieldcan be used to independently tune the bandwidth and band gaps in twistedbilayer graphene, opening up the intriguing possibility to engineerbands and enabling access to novel correlated phases in a larger rangeof twisted homobilayers


Clostridioides difficile infection (rCDI) in adults. As the first FDA-approved microbiota product, this new agent may pose challenges in administration, particularly with Infectious Disease (ID) or other specialties not typically providing rectally administered therapies. As part of an ongoing real-world study of RBL, the purpose of this study is to develop and report a simple protocol for the administration of RBL in clinical practice.Fecal Microbiota, live-jslm (RBL) is a rectally administered, pre-packaged, live biotherapeutic approved in November 2022 for the prevention of recurrence of We reviewed electronic health records, administration records and internal databases for patients receiving RBL since February 2023. Records were reviewed for patient demographics, setting of care, time from order to treatment, logistics from order to administration and payor details.Six rCDI patients  have received RBL; 1 treated in an ID practice and the other 5 in GI practices. Following insurance approval and scheduling of the patient, RBL was ordered from the distributor and shipped to the practices in a 150mL pre-packaged frozen suspension. RBL was thawed for 24 hours and administered within 5 days. Average time from order to treatment was 18±5 days. Administration of RBL was performed by registered nurses or licensed vocational nurses. Reported RBL administration time was 5 minutes, with an additional 15 minutes for observation. Medicare (MCR) was the most common payor (71%) with traditional MCR (n=3), MCR Advantage (n=2), and one commercially insured. There have been no payor denials. Criteria for approval differed slightly between payors, but all required at least 1 prior episode of CDI. All plans required prior authorization except traditional MCR. Reimbursement was adequate for both the medication and instillation protocols.Early experience with RBL administration found more treatment by GI than ID physician practices. Authorizations were granted as expected with the administration and visit surprisingly brief and simple. RBL holds promise as a feasible office-based therapy for prevention of rCDI.Jonathan A. Rosenberg, MD, Aimmune: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant Timothy E. Ritter, MD, Abbvie: Advisor/Consultant|Ardelyx: Advisor/Consultant|Arena: Advisor/Consultant|Boehringer Ingelheim: Advisor/Consultant|Bristol Myers Squibb/Celgene: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Ferring: Advisor/Consultant|Ferring: Data Adjudication Committee|Genetech/Roche: Advisor/Consultant|Gilead: Advisor/Consultant|Intercept: Advisor/Consultant|Iterative Scopes: Expert Testimony|Iterative Scopes: Ownership Interest|Janssen: Advisor/Consultant|Nestle/Seres: Advisor/Consultant|Pfizer: Advisor/Consultant|Prometheus: Advisor/Consultant|Rebiotix: Data Adjudication Committee|Sanofi: Advisor/Consultant|Takeda Pharmaceuticals: Advisor/Consultant Lucinda J. Van Anglen, PharmD, ADMA Biologics, Inc.: Grant/Research Support|Ferring Pharmaceuticals: Grant/Research Support|Novartis: Grant/Research Support|Octapharma: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support Amy Guo, PhD, Ferring Pharmaceuticals: Employee Mielad Moosapanah, PharmD, Ferring Pharmaceuticals: Employee Min Yang, MD, PhD, Analysis Group, Inc.: I am an employee of Analysis Group, Inc., which has received consulting fees from Ferring for the conduct of this study. Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|Ferring: Advisor/Consultant|Paratek: Grant/Research Support