Plant-microbe interactions in the rhizosphere shape carbon and nitrogen cycling in soil organic matter (SOM). However, there is conflicting evidence on whether these interactions lead to a net loss or increase of SOM. In part, this conflict is driven by uncertainty in how living roots and microbes alter SOM formation or loss in the field. To address these uncertainties, we traced the fate of isotopically labeled litter into SOM using root and fungal ingrowth cores incubated in a Miscanthus x giganteus field . Roots stimulated litter decomposition, but balanced this loss by transferring carbon into more persistent, aggregate associated SOM. Further, roots selectively mobilized nitrogen from litter without additional carbon release. Overall, our fundings suggest that roots can efficiently mine nitrogen and build persistent soil carbon.

By regulating carbon uptake and water loss by plants, stomata are not only responsible for productivity but also survival during drought. The timing of stomatal closure is crucial for preventing excessive water loss during drought, yet has high ecological variability between species. An aspect of stomatal response that remains disputed is the mechanism driving the trigger for stomatal closure during drought. We investigated this in a highly embolism resistant tree species Umbellularia californica. We tracked leaf endogenous abscisic acid (ABA) levels and determined the predawn and midday leaf water potential and gravimetric soil water content (gSWC) thresholds for stomatal closure and transpiration decline during a progressive drought. We found that while U. californica plants have a peaking type ABA dynamic where ABA levels rise early in drought then decline under prolonged drought conditions. The early increase in ABA levels corresponded to the closing of stomata and reduced transpiration. Furthermore, we found that the gSWC at which transpiration declines occurs before any large decreases in soil and predawn plant water status and could best be explained by declines in midday water potentials along with increased ABA levels. Our results indicate that ABA mediated stomatal regulation is an integral mechanism for delaying whole plant dehydration and can occur with minimal changes in bulk soil and plant water status.

This is a very first attempt to study various parameters of a medicinal plant, Delphinium suave Huth. The plant is erect, geophytic, herbaceous, with tuberous root, trifid in a palmatipartite, strigose cuneate leaf and white spurred zygomorphic flower. The root was isodiametric phellem with single non-glandular trichomes. The stem revealed single-layered cuticle, multiseriate epidermis, cortex, pith ray and uniserate bowed non-glandular trichomes. The leaf was amphistomatic, showed tapering trichomes, prismatic crystals and ranunculaceous stomata with circumference 144.66-182.67 µm. Pollen grains in Light Microscopy (LM), were prolate, spheroidal trizonocolpate, isopolar, radiosymmetric, scabrate, elliptic and monads. Scanning Electron Microscope (SEM) pollen surface was scabrate, monad, size varied from 18.06 µm-16.67µm, colpus to inaperturate, tricolpate, ornamented, echinus, isopolar, isodiametric and circular. SEM roots showed sclerenchymatic tissues, stellate, glandular, non-glandular trichomes and crystals. The stem showed scalariform, pitted vessels, warty protuberances, unicellular, silicified, non-glandular trichomes. Leaves powder revealed, simple, unicellular, tapered headed, uniseriate, sessile, capitate, unbranched glandular, non-glandular, trichomes with crystals. Capitate, stellate, circular, unicellular, branchy trichomes were observed for the first time through SEM. Powder drug study of root, stem leaves through LM also revealed different tissues. Preliminary phytochemical revealed alkaloids, anthocyanins, anthraquinones, coumarins, flavones, mucilages, saponins, steroids, terpenoids, volatile oils and proteins. GC/MS showed 36 compounds in roots 33 in stem while 41 in leaves. Fluorescence analysis of roots, stem and leaves showed variation in colour when treated with chemicals. This study will assist pharmacognostic exploration, authentication from adulterants/allied species for consistent quality, resulting in safe use, preservation and efficacy.

Lumpy skin disease virus has infected cows across the world resulting in the death or destruction of at least a million cows. Poxviridae family includes 88 such viruses that cause deadly diseases like smallpox, monkeypox and lumpy skin disease. Pox virus induced infections have been known to be sporadic and zoonotic. We identified two novel protein kinases in poxviridae genomes. Multiple sequence alignment and phylogenetic analysis of these pox viral protein kinases revealed the sequence conservation and evolutionary relationships of these viral protein kinases. AI driven methods revealed 3D structures and active site of the two protein kinases. The viral kinases also showed remarkable structural conservation. Virtual screening of pox virus kinases identified LSTK and LYK as druggable targets and 2 FDA approved kinase inhibitors (lapatinib and pazopanib) were recognized as potential inhibitors of LSTK and LYK. Molecular dynamics simulations identified these inhibitors to be competitive inhibitors of the new kinases. These findings provide valuable insights that can be leveraged in the development of antiviral therapeutics for pox virus infections LSDV and Monkeypox.

Since the publication of the last Cellular Therapy and Stem Cell Transplant blueprint in 2013, Children’s Oncology Group cellular therapy-based trials for advanced the field and created new standards of care across a wide spectrum of pediatric cancer diagnoses. Key findings include that tandem autologous transplant improved survival for patients with neuroblastoma and atypical teratoid/rhabdoid brain tumors, one umbilical cord blood (UCB) donor was safer than two UCB donors, killer immunoglobulin receptor (KIR) mismatched donors did not improve survival for pediatric acute myeloid leukemia when in vivo T cell depletion is used and the depth of remission as measured by next-generation sequencing based minimal residual disease assessment pre-transplant was the best predictor of relapse for acute lymphoblastic leukemia. Plans for the next decade include optimizing donor selection for transplants for acute leukemia/myelodysplastic syndrome, using novel engineered cellular therapies to target a wide array of malignancies, and developing better treatments for cellular therapy toxicities such as viral infections and graft-vs-host disease.

Background and Purpose: The holotoxin A1, isolated from Apostichopus japonicus, has shown potent antifungal activities with unclear mechanism and efficacy against candidiasis. This study aimed to reveal the antifungal effects and mechanism of holotoxin A1 against Candida albicans in vitro and in candidiasis murine models for the first time. Experimental Approach: The antifungal effect of holotoxin A1 against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A1, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. The oropharyngeal and intra-abdominal candidiasis mouse models were used to verify the effectiveness and systematic toxicity in vivo. Key Results: Holotoxin A1 was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A1 inhibited the oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A1 caused the disfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A1 directly inhibited the enzymatic activity of mitochondrial complex I (CI) and antagonized with the rotenone, an inhibitor of CI, against C. albicans. Meanwhile, the CI subunit NDH51 null mutants showed the decreased susceptibility to holotoxin A1. Furthermore, holotoxin A1 significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis murine models. Conclusions and Implications: Holotoxin A1 was a promising candidate for the development of novel antifungal drug against both oropharyngeal and intra-abdominal candidiasis, especially caused by the drug resistant strains.

We aimed to assess the association of household and classroom determinants with students’ school absence due to respiratory tract infections (RTI) among 253 students (4-11 years) of 20 classrooms. We collected 71 absences; RTI incidence was very high during the study period, 17.5-33.1 cases per 100 population. Having someone else at home with respiratory symptoms was the most significant epidemiological factor (OR=9.12, CI 95%=2.54-33.39), suggesting that households are crucial for the transmission of RTI to the children. A positive but not statistically significant association was observed between higher median levels of CO2 and respiratory-related absences (OR=1.2, CI 95%=0.98-1.46).

Background We used data from a prospective cohort to explore two-year trajectories of “long COVID” (persistent symptoms after SARS-CoV-2 infection) and their association with illness perception. Methods RECoVERED participants (adults; prospectively enrolled following laboratory-confirmed SARS-CoV-2 infection, May 2020-June 2021) completed symptom questionnaires at months 2-12, 18 and 24, and the Brief Illness Perception Questionnaire (B-IPQ) at months 1, 6, and 12. Using group-based trajectory models (GBTM), we modelled symptoms (mean total numbers and proportion with 4 specific complaints), including age, sex, BMI and timing of infection as covariates. In a multivariable linear mixed-effects model, we assessed the association between symptom trajectories and repeated B-IPQ scores. Results Among 292 participants (42% female; median age 51 [IQR=36-62]), four trajectories were identified, ranging from Trajectory 4 (8.9%; 6+ symptoms) to Trajectory 1 (24.8%; no symptoms). The occurrence of fatigue and myalgia increased among 23% and 12% of participants, respectively. Individuals in Trajectory 4 experienced more negative adjusted B-IPQ scores over time than those in Trajectories 1-3. Conclusions We observed little fluctuation in the total number of symptoms but individual symptoms may develop as others resolve. Reporting a greater number of symptoms was congruent with more negative illness perception over time.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterised by oculocutaneous albinism, a bleeding diathesis and platelet storage deficiency. The aim of this paper is to report a case of a patient with HPS who was followed over a decade. A 2-and-a-half-year-old boy presented with recurrent respiratory tract infections and

Heart Failure due to Peripartum Cardiomyopathy Presenting in the First Week of Puerperium - A Case Series from NepalAbstract: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. Most of the clinical presentation is similar to symptoms of advanced pregnancy making the diagnosis difficult. Reported are three patients who developed dyspnea, orthopnea, and dry cough during the first week of puerperium. On examination, bilateral lower limb edema and bilateral basal lung crepitation were present in all patients. Chest radiograph showed pulmonary edema in cases two and three, and pleural effusion in case one. All patients had reduced left ventricular ejection fraction and raised N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels. Case two developed PPCM in the background of left pyelonephritis. Case three was complicated by acute kidney injury. All patients were managed with bromocriptine, diuretics, beta-blockers, ACE inhibitors, and fluid restriction. Hence, PPCM though rare should be considered as a differential in women presenting with features of heart failure in later months of pregnancy or within five months of delivery.Keywords: heart failure, bromocriptine, peripartum dilated cardiomyopathy, pregnancy, peripartum cardiomyopathy.Introduction-Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure affecting women in the later months of pregnancy or within five months of delivery. PPCM often presents when peak volume load, reached just before delivery is greatly reduced after delivery.1,2PPCM affects women from all ethnicities globally with wide variation in incidence from 1:20,000 live births in Japan to 1:100 in Zaria, Nigeria.3,4 With a prognosis that can vary from the complete recovery of left ventricular function to maternal mortality as well as recurrence with subsequent pregnancies, the study of PPCM has been done sparsely in Nepal.2,5 This case series attempts to increase awareness of disease, diagnosis, and treatment in Nepal.CASE PRESENTATIONCase 1A 33-years lady, G2A1 at 38+6 weeks of gestation, with no significant medical history underwent emergency LSCS for non-progression of labor secondary to arrest of descent. On the 4th day of puerperium, she developed dyspnea on exertion, orthopnea, bilateral lower limb edema, and dry cough. On examination, she had increased blood pressure (160/110 mmHg) and bilateral lower limb pitting edema with bilateral basal crepitation on chest auscultation. Chest radiograph showed bilateral minimal pleural effusion. Transthoracic echocardiography (TTE) showed severe left ventricular systolic dysfunction, dilated left atrium (LA), moderate to severe mitral regurgitation (MR), severe tricuspid regurgitation (TR), moderate pulmonary artery hypertension (PAH) and reduced ejection fraction i.e< 25%. ECG showed T wave inversion in leads V1-V4 and aVL (figure 1). Serum N-terminal pro-b-type natriuretic peptide (NT-proBNP) was 10897 pg/ml (Normal <300). With the diagnosis of PPCM, she was managed with fluid restriction, diuretics, beta blockers, angiotensin receptor blockers (ARB), bromocriptine, and antibiotics. Repeat TTE done on the 12th day of puerperium showed EF of 30%. However, she had 3 episodes of syncopal attack on the 19th puerperal day which was probably due to orthostatic hypotension. She was discharged on the 22nd puerperal day with oral ARB and bromocriptine and with close follow-up with cardiology and obstetrics and gynecology clinic.

A Giant Hydronephrosis Disguised as Abdominal Obesity

Spices and herbs play an important role in our day to day life with its application varying from flavouring the food to various medicinal uses. But the major limitations linked with these nature oriented spicesare individualized and restricted information about the identification and quality mapping. With increasing demands, adulteration of spices and herbs become a major problem for all the stakeholders . Artificial intelligence based machine learning and deep learning models have already been implemented in the various ways for the identification of herbal images in real time basis. Evidence from past studies related to identification of plants images strengthens our concept for the implementation of the artificial intelligence in the spice sector for the adulteration identification which can become pioneer step in solving the problem of adulteration. There are various opportunities for advancement in producing a robust model for the identification of spices accurately in real time basis. In this review paper, various reliable and efficient machine learning algorithms for herbs and spice image classification has been reviewed. Techniques involved forpreparation of such model have been discussed in details for the better understanding of readers. With inclusion of various globally available herbal image datasets and review of recent research related to plants image identification through machine learning, this article also explains various machine learning model such as artificial neural network, convolutional neural network etc along with different parameters involved in the authentication of the developed model to devise an artificial intelligence based methodology for quality assessment of herbs and spices.

Broadband surface-enhanced infrared absorption (SEIRA) spectroscopy is crucial for achieving high-sensitivity in the detection of complex analyte. A new design of Six-pointed Asterisk NanoAntenna (SANA) array is proposed to enhance signal-to-noise ratio of SEIRA spectroscopy. The SANA structure offers elevated design freedom in terms of resonance amplitude and frequency. The measurement data clearly demonstrates that our device has the most uniform resonance coverage over 390 cm -1. The broadband resonance uniformity directly benefits the signal-to-noise ratio enhancement across six fingerprints of alanine. Our SEIRA nanoantenna array design method serves as an effective approach for broadband and dense fingerprints detection. For example, it enables the simultaneous measurement of amide I and amide II, allowing for more comprehensive analysis of biomolecules.

A document by Alisha Yadav. Click on the document to view its contents.

Due to the characteristics of efficient transmission method, Orthogonal Frequency Division Multiplexing (OFDM) becomes the key technology of the mobile communication network. The channel estimation (CE) is employed in channel conditions at which there is a need for time-varying features. To overcome the complexity of CE technique, this work integrates the Linear Time Invariant (LTI)-Weiner filter model based Least Square estimation (LS)-Discrete Fourier Transform (DFT). A 128-QAM modulation is applied to attain the Channel State Information (CSI) for coherent demodulation. The input binary data encoded by Space Time Block coding (STBC) technology and is being modulated by 128-QAM modulator. The pilot insertion is responsible for decreasing the spectral efficiency more effectively if the channel is a high frequency selective one or time-invariant one. IFFT transforms the signal to compressed form after which the estimated input stream is transmitted over Additive White Gaussian Noise (AWGN) for the transmission purpose. At the receiver side, the received data is demodulated by 128-QAM and decoded by STBD to attain original information. The performance of channel estimation is carried in terms of Bit Error Rate (BER), complexity and throughput which is compared with traditional methods to highlight the benefit of proposed method.

Adiponectin is an antidiabetic endogenous adipokine that have protective role in unfavorable metabolic sequalae arising from obesity. Recent evidence suggests a sinister link between hypoadiponectinemia and development of insulin resistance/ type 2 diabetes (T2D). The insulin sensitizing property of adiponectin is through specific adipoq receptors R1 & R2, activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α pathways. AdipoAI is a novel synthetic analogue of endogenous adiponectin with possibly similar pharmacological effects. Thus, there is a need of orally active small molecules that activate Adipoq subunits, and its downstream signaling could ameliorate obesity related type 2 diabetes. This study was aimed to access the effects of AdipoAI on obesity and T2D. Through in-vitro and in-vivo analyses, we investigated the anti-diabetic potentials of AdipoAI and compared it with AdipoRON, another orally active adiponectin receptors agonist. Our results showed that In-vitro treatment of AdipoAI (0-5µM) increased adiponectin receptor subunits AdipoR1/R2 with increase in AMPK and APPL1 protein expression in C2C12 myotubes. Similarly, in-vivo, oral administration of AdipoAI (25 mg/kg) observed similar effects as that of AdipoRON (50 mg/kg) with improved control of blood glucose and insulin sensitivity in diet-induced obesity (DIO) mice models. Further, AdipoAI significantly reduced epididymal fat content with decrease in inflammatory markers and increase in PPAR-a and AMPK levels and exhibited hepatoprotective effects in liver. Further, AdipoAI and AdipoRON also observed similar results in adipose tissue. Thus, our results suggest that low doses of orally active small molecule agonist of adiponectin AdipoAI can be a promising therapeutic target for obesity and T2D.

Phylogenetic studies now routinely require manipulating and summarizing thousands of data files. For most of these tasks, currently available software requires considerable computing resources and substantial knowledge of command-line applications. We develop ultrafast and memory-efficient software that performs over a dozen common phylogenomic manipulations and calculates statistics summarizing essential data features. Our software is available as standalone command-line (CLI) and graphical user interface (GUI) applications, and as a programming language library for Rust, R, and Python, with possible support of other languages. The CLI and library versions, SEGUL, run native on Windows, Linux, and macOS, including Apple ARM Macs. The GUI version extends support to include mobile iOS and Android operating systems. SEGUL offer fast execution times and low memory footprints regardless of dataset size and platform choice. The inclusion of a GUI minimizes bioinformatics barriers to phylogenomics while SEGUL’s efficiency reduces economic barriers by enabling analysis on inexpensive hardware. Our support for mobile operating systems further enables teaching phylogenomics where access to computing power is limited.

IntroductionEndoscopic removal of colorectal polyps is used as first-line treatment for reducing incidence of colorectal cancer and cancer-related mortality.(1) Colonoscopy is a safe procedure in general but there is a chance of complication. Complications are more likely to happen in colonoscopy with cautery. As the procedure gets more complex, the higher rate of complications is reported.(2) Perforation and post-colonoscopy hemorrhage are the most common complications.Local infection is one of colonoscopy complications; however, it is rare indeed. Perianal abscess and Fournier’s gangrene have been described after colonoscopy. The mechanism is local mechanical trauma.(3) Intraperitoneal and retroperitoneal abscess formation are also described in a few case reports as a result of colonoscopy.(4, 5) As far as we know, there is no report of rectus abdominis muscle abscess after colonoscopy. In this article, we want to present a case of rectus abdominis muscle abscess after colonoscopy completed with applying abdominal pressure techniques.

In order to raise the hardness and strength of the surface layer of mechanical components and induce favourable residual compressive stresses, case-hardening procedures have become established in the heat treatment of steel. In this work, a calculation concept for the fatigue strength of components that have been case-hardened through carburizing heat-treatment is being developed. The residual stress and the load stresses in complex-shaped, carburized materials are determined using a finite element (FE) model. The fatigue limit of the components is derived using probabilistic methods and taking into account hardness gradients, residual stresses, and non-metallic inclusions. The model is validated with available axial bending fatigue test data and then used to predict the rotating bending fatigue limit of samples with various geometries and heat-treatment conditions. This work demonstrates the capability of combining probabilistic and FE-based modelling to represent complex interactions between variables that affect the fatigue of heat-treated components, such as steel cleanliness, notch shape, case-hardening depth, or loading conditions.

Background: Previous case studies have reported reversal of acute renal failure after pericardiocentesis in pericardial effusion. This study examines the effects of pericardiocentesis on pre-procedural low cardiac output and acute renal dysfunction in patients with pericardial effusion. Methods: This is a retrospective study of 95 patients undergoing pericardiocentesis between 2015 and 2020. Pre- and post-procedure transthoracic echocardiograms (TTE) were reviewed for evidence of cardiac tamponade, resolution of pericardial effusion, and for estimation of right atrial (RA) pressure and cardiac output. Laboratory values were compared at presentation and post-procedure. Patients on active renal replacement therapy were excluded. Results: Ninety-five patients were included for analysis (mean age 62.2±17.8 years, 58% male). There was a significant increase in glomerular filtration rate pre- and post-procedure. Fifty-six patients (58.9%) had an improvement in glomerular filtration rate after pericardiocentesis (termed “responders”), and these patients had a lower pre-procedure glomerular filtration rate than “non-responders”. Forty-four patients (46.3%) had a greater than 10% improvement in glomerular filtration rate. There was a significant improvement in estimated cardiac output and right atrial pressure for patients in both groups. Patients who had an improvement in renal function had significantly lower pre-procedural diastolic blood pressure and mean arterial pressure. Conclusions: Pericardial drainage may improve effusion-mediated acute renal dysfunction by reducing right atrial pressure and thus systemic venous congestion, and by increasing forward stroke volume and perfusion pressure.

Service desk systems have a vast and rich base of information, consisting of the history of calls made, which can and should be used as a reference base for subsequent calls. Common search tools, such as keyword searches, prove to be unfeasible in large datasets, in addition to being able to bring results not necessarily related to the problem. “State-of-the-art” techniques exist, but they require high computational and operational costs for their training and use. In this sense, the purpose of this work is to investigate the sensitivity of machine learning algorithms in finding the characteristic defined here as “relevance”: the characteristic of texts with knowledge that can be reused. The motivation is that non-relevant texts can be removed in advance from the database, allowing complex algorithms to be employed in a more condensed database, reducing computational costs. Tests were performed with several combinations between the TF-IDF vectorizer and the word embedding Doc2Vec and the classic classifiers Naive-Bayes, Adaptive Boosting, Random Forest, Stochastic Gradient Descent, Logistic Regression, Support Vector Machine and Light Gradient Boosting Machine, and the classifier TextConvoNet, an architecture based on Convolutional Neural Networks. The TextConvoNet classifier presented the best results, with metrics close to 0.93, showing that the concept is detectable and that the technique is viable for removing non-relevant texts from a database.

An efficient and linear power amplifier (PA) for millimeter wave applications using a 130nm CMOS process is presented in this paper. The proposed PA uses transformer coupling for output, inter-stage, and input matching and also utilizes inter-stage inductors to boost RF achievement. The Ansoft high-frequency structure simulator (HFSS) is used to analyze and design the coupling transformers and inter-stage matching inductors to achieve a high coupling coefficient and quality factor over the frequency range of 19 to 29 GHz. The 2 nd harmonic termination networks are connected at each stage of the proposed power amplifier to enhance the gain and efficiency. The suggested radio frequency power amplifier consists of three stages, the input stage operates in class-B operation to increase the efficiency without an influence on the DC power consumption, while the driver and power stages work in class-AB to improve the RF output power. Also, the power stage is a parallel combination of class-B and class-AB to improve the one-dB compression point and enhance the linearity. The proposed RF power amplifier operates in the frequency range from 19 to 29 GHz. The suggested PA achieves a saturated output power of 15.1 dBm, a maximum power added efficiency (PAE) of 19.35 %, and a peak power gain of 22.72 dB. Moreover, the peak output 1-dB compression point for the proposed power amplifier is 13.1 dBm and consumes a DC power of 98.09 mW. Lastly, the die and overall areas of the suggested power amplifier are 0.4 mm 2 and 0.67 mm 2, respectively.

Anju Murayama1*Affiliation: 1 School of Medicine, Tohoku University, Sendai City, Miyagi, Japan*Corresponding authorCorrespondenceAnju MurayamaSchool of Medicine, Tohoku University, Sendai City, Miyagi, JapanTelephone: +81-22-717-8006Email address: ange21tera@gmail.comFunding sources: NoneConflicts of Interest: None declared.IRB approval status: Not applicablePatient informed consent: Not applicableKeywords: general dermatology; industry payments; Open Payments Database; Sunshine Act; conflicts of interest; ethics

Abstract: RationaleHealthcare industry sometimes make large marketing payments to physicians. Previous studies have demonstrated that there are significant associations between industry marketing practices and physicians’ prescribing behaviors in several specialties. Given that current increasing introduction of many novel biologics for atopic dermatitis and increasing payments to dermatologists, the industry payments to dermatologists for atopic dermatitis drugs could be associated with their prescribing patterns in the United States.  Aims and objectives:This study aims to evaluate association between dermatologists’ dupilumab prescription behaviors and manufacturer’s sponsored meal payments to dermatologists in the United States.  Method Using the Centers for Medicare and Medicaid Services and the Open Payments Database, this cross-sectional analysis evaluated associations between manufacturer’s sponsored meal payments to dermatologists related to dupilumab and dermatologists’ dupilumab prescriptions between 2017 and 2021. Associations were evaluated using logistic generalized estimating equations (GEE) and negative binomial regression GEE models at individual dermatologist level.  ResultsAmong 2852 dermatologists prescribing dupilumab, 74.5% received meal payments, amounting to $1,083,919 between 2017 and 2021. Dermatologists receiving meal payments were more likely to prescribe dupilumab (odds ratio 1.50, 95% CI: 1.37-1.65). There were also consistent dose-response associations between meal payments and total claims as well as Medicare spending. Dermatologists who received 1, 2-5, 6-10, and 11-15 meal payments per year reported 1.13 (95% CI: 1.03 – 1.24, p<0.05), 1.35 (95% CI: 1.24 – 1.46, p<0.001), 1.64 (95% CI: 1.48 – 1.82, p<0.001), and 2.10 (95% CI: 1.78 – 2.47, p<0.001) times more dupilumab-related claims in the year when they received the payments than those who did not receive the payments, respectively. ConclusionThis study found that significant associations between industry-sponsored meal payments and increased dupilumab prescriptions, shedding light on the potential influence of financial relationships on clinical practice. The findings call for heightened awareness among dermatologists, patients, and policy makers regarding the impact of these relationships on healthcare expenditures and decision-making in the United States. Future research is warranted to further explore these associations longitudinally.  IntroductionDupilumab, the first biologic approved for moderate-to-severe atopic dermatitis (AD) in 2017, demonstrates both clinical and economic efficacy in the treatment of the disease:1,2 however, it may impose a financial burden on patients. Additionally, four novel drugs such as ruxolitinib (approval date: September 2021), tralokinumab (approval date: December 2021), abrocitinib (approval date: January 2022), upadacitinib (approval date: January 2022) were approved for AD in the United States.3 Nevertheless, no head-to-head clinical trials have been conducted to evaluate the safety and efficacy of these drugs, and there is no consensus on which drugs are more suitable than others and who should receive them.3 Thus, the importance of engaging in shared decision-making with patients cannot be overstated.  The increasing introduction of novel AD drugs has led to fierce competition among the manufacturers and increased marketing activities to dermatologists, as a previous study showed that mean non-research payments from the healthcare industry to dermatologists increased by 11.7% each year.4 Prior investigations have shown that there are significant associations between industry payments to physicians and physicians’ prescribing behaviors in several specialties other than dermatology.5-12 However, to date, no research has explored the association between industry payments to dermatologists and their clinical practices. This study aimed to evaluate the associations between industry payments to dermatologists related to dupilumab and their dupilumab prescribing patterns in the United States.  MethodsThis cross-sectional analysis examined the association between the industry payments to dermatologists and their prescriptions and Medicare expenditures for dupilumab in the United States, using the Centers for Medicare and Medicaid Services and Open Payments Database. As of March 2023, the 2021-Medicare Part D file was the latest available, analyzable dataset. Of the three biologic therapies approved for AD in the United States, only dupilumab was prescribed by more than 20 physicians. Given these circumstances, this study evaluated only the association between industry payments to dermatologists and the dermatologists’ dupilumab prescribing patterns. All dermatologists who prescribed more than 10 claims of dupilumab in a single year between 2017 and 2021 were identified from the publicly accessible Medicare Part D database. The publicly accessible Medicare Part D database only includes information of prescribers who reported more than 10 claims for a drug in a single year, to protect patients’ privacy.13 Then, matching the extracted dermatologist prescribers’ National Provider Identifier numbers, general payments for food and beverage (hereby meal payments) to the dermatologists were extracted from the Open Payments Database between 2017 and 2021, as previously noted.7,14-17 This study only considered meal payments, as previous studies showed that, of several payment categories, meal payments were strongly associated with increased drug prescriptions and healthcare costs in the United States.6,8,13,18,19  The association between meal payments for dupilumab and the dupilumab prescriptions was evaluated using a logistic generalized estimating equation (GEE), adjusting for the covariates including gender, practice region, years in practice, the graduated medical schools, and payment/prescribed year.7 Furthermore, the associations between the number of payments and the total number of 30-day standardized claims and Medicare expenditures were examined using negative binomial regression GEE models, because the prescription variables were highly skewed, as in a previous study.6,20 The number of annual meal payments per physician was categorized into six groups: no payment, one payment, 2-5 payments, 6-10 payments, 11-15 payments, and more than 15 payments. All statistical analyses were performed using Python 3.9.12 (Python Software Foundation, Beaverton, OR, USA), Microsoft Excel, version 16.0 (Microsoft Corp., Redmond, WA, USA), and Stata version 17.0 (StataCorp, College Station, TX, USA). This study only considered publicly available information and was designed as a non-human subjects study, ethical review and approval were not required.  ResultsA total of 2852 dermatologists prescribed 146,324 claims of dupilumab entailing $470.0 million in Medicare expenditures between 2017 and 2021. Among them, 74.5% received 39,859 meal payments associated with dupilumab, totaling $1,083,919 during the same period. The average number of meal payments per dermatologist per year was 5.3, with an average cost per meal of $27.2.  Dermatologists receiving meal payments were more likely to prescribe dupilumab with an odds ratio of 1.50 (95% confidence interval [CI]: 1.37-1.65, p<0.001 in the year they received the payment compared to those who did not receive meal payments. Additionally, there were consistent dose-response associations between the number of industry-sponsored meals for dupilumab and the total claims (Figure 1A) and total Medicare spending (Figure 1B) at the individual dermatologist level. Dermatologists who received 1, 2-5, 6-10, and 11-15 meal payments per year reported 1.13 (95% CI: 1.03 – 1.24, p<0.05), 1.35 (95% CI: 1.24 – 1.46, p<0.001), 1.64 (95% CI: 1.48 – 1.82, p<0.001), and 2.10 (95% CI: 1.78 – 2.47, p<0.001) times more dupilumab-related claims in the year when they received the payments than those who did not receive the payments, respectively (Table 1). Similarly, dermatologists who received 1, 2-5, 6-10, and 11-15 meal payments reported 1.16 (95% CI: 1.04 – 1.29, p<0.01), 1.40 (95% CI: 1.28 – 1.53, p<0.001), 1.75 (95% CI: 1.56 – 1.96, p <0.001), and 2.28 (95% CI: 1.90 – 2.73, p<0.001) times higher Medicare expenditures related to dupilumab than those who did not, respectively (Table 1). Adjusted mean annual Medicare expenditures for dupilumab were $30,408 (95% CI: $28,416 – $32,400) in dermatologists without payments, $36,385 (95% CI: $32,496 – $40,274) in dermatologists with one meal payment, $44,674 (95% CI: $41,151 – $48,198) in dermatologists with 2-5 meal payments, and $57,486 (95% CI: $51,453 – $63,520).  DiscussionThis study represents the first analysis elucidating the associations between industry-sponsored meal payments to dermatologists and their prescription patterns for dupilumab in the United States. This study found that there were strongly significant associations between industry-sponsored meal payments to dermatologists related to dupilumab and the dermatologists’ dupilumab prescriptions in the United States. These findings were consistent with numerous previous studies in other specialties.5,6,10-12,18,19,21 Additionally the findings highlight the potential influence of industry payments to dermatologists on their clinical practice, though dupilumab significantly improves quality of life and disease control in patients with moderate-to-severe AD.1,2  Furthermore, novel drugs for severe atopic dermatitis, such as tralokinumab, abrocitinib, and upadacitinib, have been introduced for the past few years,3 but the lack of direct head-to-head evidence of the safety and efficacy of these new drugs has led to fierce marketing competition and increasing marketing activities to physicians among the manufacturers.4 With the increasing introduction of novel drugs, marketing costs to dermatologists may increase, and dermatologists' treatment choices may be further influenced by information provided by pharmaceutical manufacturers and/or payments and meal provided by the manufacturers. To evaluate this hypothesis, we need further longitudinal research on associations between industry payments to dermatologists and the dermatologists’ clinical practice. The association between industry payments to dermatologists and dermatologists’ prescribing patterns does not necessarily mean inappropriate prescriptions influenced by the healthcare industry. Also, the associations were not necessarily causality, as this study is observational cross-sectional analysis. Patients may want to know that many dermatologists receive non-research payments from the healthcare industry and that there are associations between these payments and dermatologists' prescribing patterns, as shown in previous studies.22-25 Nevertheless, very few patients and people are aware that their physicians received industry payments, these payments could influence physicians’ clinical practice, and the payment information is available from the US government online database.24,26 Since January 2023, physicians licensed in California are legally required to notify their patients about payment information disclosed in the Open Payments database. Transparency is one of the key aspects improving patient-centered care and can foster shared decision-making with patients.27 Thus, all dermatologists should be transparent in their financial relationships with the healthcare industry, disclose these information to their patients and integrate into shared decision-making process when discussing treatment options with patients .  However, this study has several limitations. First, this observational study can only establish associations and not necessarily causality between payments and dermatologists' prescriptions. Second, there may be unmeasured confounding factors, such as the patient number and the content and reasons behind the payments provided to the dermatologists.14-16 Additionally, this study exclusively relied on prescription data from the Medicare Part D database, which may have led to underestimations of the prescription amounts of dupilumab.6,13,18 In conclusion, at least, this study provided to all dermatologists, patients, and policy makers that the industry sponsored meal payments to dermatologists were significantly associated with higher dupilumab prescriptions and large healthcare expenditures in the United States. Thus, all dermatologists need to pay more attention to their financial relationships with the healthcare industry and the impact these relationships may have on their clinical practices. References 1.           Simpson EL, Bieber T, Guttman-Yassky E, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. Dec 15 2016;375(24):2335-2348. doi:10.1056/NEJMoa16100202.           Zimmermann M, Rind D, Chapman R, Kumar V, Kahn S, Carlson J. Economic Evaluation of Dupilumab for Moderate-to-Severe Atopic Dermatitis: A Cost-Utility Analysis. J Drugs Dermatol. Jul 1 2018;17(7):750-756. 3.           Ratchataswan T, Banzon TM, Thyssen JP, Weidinger S, Guttman-Yassky E, Phipatanakul W. Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect. J Allergy Clin Immunol Pract. Mar 2021;9(3):1053-1065. doi:10.1016/j.jaip.2020.11.0344.           Murayama A. Industry payments to dermatologists in the United States: A nine-year analysis of the Open Payments Database between 2013 and 2021. Authorea Preprints. 2023;5.           Mitchell AP, Trivedi NU, Gennarelli RL, et al. Are Financial Payments From the Pharmaceutical Industry Associated With Physician Prescribing? : A Systematic Review. Ann Intern Med. Mar 2021;174(3):353-361. doi:10.7326/M20-56656.           Inoue K, Tsugawa Y, Mangione CM, Duru OK. Association between industry payments and prescriptions of long-acting insulin: An observational study with propensity score matching. PLOS Medicine. Jun 2021;18(6):e1003645. doi:10.1371/journal.pmed.10036457.           Murayama A. Pharmaceutical industry-sponsored meals and prescriptions of biologics for asthma. J Allergy Clin Immunol Pract. May 26 2023;doi:10.1016/j.jaip.2023.05.0308.           Murayama A. Industry-sponsored meals are associated with increased prescriptions and Medicare expenditures on brand-name colchicine in the United States. Authorea Preprints. 2023;9.           Duarte-Garcia A, Crowson CS, McCoy RG, et al. Association Between Payments by Pharmaceutical Manufacturers and Prescribing Behavior in Rheumatology. Mayo Clin Proc. Feb 2022;97(2):250-260. doi:10.1016/j.mayocp.2021.08.02610.         Hollander MA, Donohue JM, Stein BD, Krans EE, Jarlenski MP. Association between opioid prescribing in Medicare and pharmaceutical company gifts by physician specialty. Journal of general internal medicine. 2020;35(8):2451-2458. 11.         Mitchell AP, Winn AN, Lund JL, Dusetzina SB. Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology. https://doi.org/10.1634/theoncologist.2018-0423. The Oncologist. 2019/05/01 2019;24(5):632-639. doi:https://doi.org/10.1634/theoncologist.2018-042312.         Fleischman W, Agrawal S, Gross CP, Ross JS. Association of Pharmaceutical Manufacturer Payments to Physicians and Prescribing Dosage of Opioids. J Gen Intern Med. Jul 2019;34(7):1074-1076. doi:10.1007/s11606-019-04897-913.         DeJong C, Aguilar T, Tseng C-W, Lin GA, Boscardin WJ, Dudley RA. Pharmaceutical Industry–Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries. JAMA Internal Medicine. 2016;176(8):1114-1122. doi:10.1001/jamainternmed.2016.276514.         Murayama A, Kugo H, Saito Y, Saito H, Tanimoto T, Ozaki A. A Nine-year Investigation of Healthcare Industry Payments to Pulmonologists in the United States. Ann Am Thorac Soc. Mar 24 2023;doi:10.1513/AnnalsATS.202209-827OC15.         Murayama A, Kamamoto S, Kugo H, Saito H, Ozaki A. Research and Nonresearch Industry Payments to Nephrologists in the United States between 2014 and 2021. J Am Soc Nephrol. Jul 25 2023;doi:10.1681/asn.000000000000017216.         Murayama A, Hirota S. Industry payments to pathologists in the USA between 2013 and 2021. J Clin Pathol. Apr 21 2023;doi:10.1136/jcp-2023-20890117.         Murayama A, Kamamoto S, Higuchi K, Shigeta H, Ozaki A. Trend in Industry Payments to Rheumatologists in the United States During the COVID-19 Pandemic Between 2013 and 2021. J Rheumatol. Apr 2023;50(4):575-577. doi:10.3899/jrheum.22051218.         Murayama A. Industry-sponsored research funding to allergists and clinical immunologists in the United States. Ann Allergy Asthma Immunol. Jun 21 2023;doi:10.1016/j.anai.2023.06.02119.         Hartung DM, Johnston K, Cohen DM, Nguyen T, Deodhar A, Bourdette DN. Industry Payments to Physician Specialists Who Prescribe Repository Corticotropin. JAMA Network Open. Jun 1 2018;1(2):e180482-e180482. doi:10.1001/jamanetworkopen.2018.048220.         Murayama A, Hoshi M, Saito H, et al. Nature and Trends in Personal Payments Made to the Respiratory Physicians by Pharmaceutical Companies in Japan between 2016 and 2019. Respiration. 2022;101(12):1088-1098. doi:10.1159/00052657621.         Fickweiler F, Fickweiler W, Urbach E. Interactions between physicians and the pharmaceutical industry generally and sales representatives specifically and their association with physicians' attitudes and prescribing habits: a systematic review. BMJ Open. Sep 27 2017;7(9):e016408. doi:10.1136/bmjopen-2017-01640822.         Fadlallah R, Nas H, Naamani D, et al. Knowledge, Beliefs and Attitudes of Patients and the General Public towards the Interactions of Physicians with the Pharmaceutical and the Device Industry: A Systematic Review. PLoS One. 2016;11(8):e0160540. doi:10.1371/journal.pone.016054023.         Wen L. Patients can’t trust doctors’ advice if we hide our financial connections with drug companies. BMJ : British Medical Journal. 2014;348:g167. doi:10.1136/bmj.g16724.         Pham-Kanter G, Mello MM, Lehmann LS, Campbell EG, Carpenter D. Public Awareness of and Contact With Physicians Who Receive Industry Payments: A National Survey. Journal of General Internal Medicine. 2017/07/01 2017;32(7):767-774. doi:10.1007/s11606-017-4012-325.         Murayama A, Senoo Y, Harada K, et al. Awareness and Perceptions among Members of a Japanese Cancer Patient Advocacy Group Concerning the Financial Relationships between the Pharmaceutical Industry and Physicians. Int J Environ Res Public Health. Mar 15 2022;19(6)doi:10.3390/ijerph1906347826.         Stein GE, Kamler JJ, Chang JS. Ophthalmology Patient Perceptions of Open Payments Information. JAMA Ophthalmology. 2018;136(12):1375-1381. doi:10.1001/jamaophthalmol.2018.416727.         Barry MJ, Edgman-Levitan S. Shared Decision Making — The Pinnacle of Patient-Centered Care. New England Journal of Medicine. 2012/03/01 2012;366(9):780-781. doi:10.1056/NEJMp1109283