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Abstract Background This study explored similarities and differences among Chinese patients and rheumatologists in their attitudes towards and perceptions of traditional Chinese medicine (TCM) for Sjögren’s syndrome (SS), including analyzing factors that influenced their decision making. Methods An anonymous questionnaire was used to conduct a multicenter survey among patients with SS at three tertiary care medical centers in Beijing and among rheumatology clinicians at several hospitals across China. Results were analyzed using descriptive statistics. Results There were 942 valid questionnaires from patients from 31 provinces and cities in China, with a male-to-female ratio of approximately 1:14, a mean age of 48.81 years, and a median disease duration of 7 (4, 10) years. There were 320 valid questionnaires from rheumatologists, covering 30 provinces and cities in China, with a male-to-female ratio of approximately 0.87:1, a mean age of 48 years, and a median work duration of 10.5 (6, 15) years. The rheumatologists treated a median of 15 (11, 50) SS cases per month, and the median proportion of SS to all rheumatic diseases was 6.66% (6–10%). Many patients believed TCM could cure the root of the disease, and the most expected TCM therapies were TCM patent prescriptions and medicinal teas. Conversely, rheumatologists placed high value on the efficacy of TCM, and most commonly prescribed Chinese herbal decoctions. Most doctor-patient groups were positive about TCM treatment, citing the low side effects as the major advantage. Regression analysis showed that for patients over 40 years old with a course of disease > 4 years, the probability of using TCM has increased by 1–6 times; the probability of recommending TCM in clinical work of doctors who have worked for more than 15 years, TCM and integrated traditional Chinese and western medicine has increased 1–2 times. Conclusions TCM has become widely accepted and earned attention from doctor-patient groups, especially among older patients and experienced rheumatologists. However, negative prejudices and absence of accurate information about TCM treatments and SS itself require improvement. The contradiction between TCM dosage form and efficacy is a major problem, and patient demand for convenient and efficient TCM patent preparations suggests future work should focus on developing TCM patent preparations with clear compositions and mechanisms.

Grain boundaries (GBs) play a crucial role on the structural stability and mechanical properties of Cu and its alloys. In this work, molecular dynamics (MD) simulations are employed to study the effects of Fe solutes on the formation energy, excess volume, dislocations and melting behaviors of GBs in CuFe alloys. It is illustrated that Fe solute affects the structural stability of Cu GBs substantially, the formation energy of GBs is reduced, but the thickness and melting point of GBs are increased, that is, the structural stability of Cu GBs is significantly improved owing to the Fe solutes. A strong scaling law exists between the formation energy, excess volume, thickness and melting point of GBs. Therefore, Fe solid solute plays an important role in the characteristics of GBs in bi-crystal Cu.

The potential microclimatic effects of street trees are influenced by their ecological characteristics, planting patterns, and street orientations, especially in subtropical hot and humid areas. To investigate these effects, four typical street tree species in Guangzhou were selected for study during the transition seasons: Khaya senegalensis, Terminalia neotaliala, Ficus microcarpa, and Mangifera indica. Air temperature (AT), relative humidity (RH), solar radiation (SR), surface temperature (ST), wind speed (WS), and the leaf area index (LAI) were monitored. The cooling effects of these four species and the resulting improvements in human thermal comfort (HTC) were assessed. The influences of tree planting patterns and street orientations on cooling benefits were systematically analyzed. The results indicate that, during transition seasons, the four street trees, on average, can block 96.68% of SR, reduce AT by 1.45 °C and ST by 10.25 °C, increase RH by 5.26%, and lower the physiologically equivalent temperature (PET) by 8.34 °C. Terminalia neotaliala, reducing AT and PET by 1.76 °C and 12.4 °C, respectively, offers the greatest potential for microclimate improvement. Among the four tree species, the variations in ST (ΔST) and PET (ΔPET) were minimal, at only 0.76 °C and 0.25 °C, respectively. The average differences in AT and PET between inter-tree and under-tree environments were 0.06 °C and 0.98 °C, respectively. The AT reduction rate was 1.7 times higher in the double-row planting pattern compared to the single-row planting pattern. Street trees planted in the northwest–southeast (NW-SE) orientation exhibited a 16.96% lower WS reduction than those in other orientations. The northeast–southwest (NE-SW) orientation showed the least potential to enhance human thermal comfort. Compared to NE-SW, the northwest–southeast (NW-SE) orientation achieved twice the rate of AT reduction, while the north–south (N-S) orientation improved it by 1.3 times. This data analysis aids in assessing the impact of green infrastructure on urban climates and demonstrates the year-round microclimatic benefits of street trees.

In view of the problem that vibration of superstructures under vibration loads of metro trains causes, this research used a metro depot and superstructure project as its background and proposed a numerical simulation method based on the impedance analytical model and finite element model to simulate and predict the vibration and secondary noise response of subway trains affecting multi-story buildings at different locations on the ground and in the superstructure. The method’s accuracy was verified using real measurement data. The research shows that vibrations generated by subway operations vertically at lower floors remain relatively unchanged, then slowly attenuate before increasing near the top floors. Mitigation measures should primarily address four aspects: rails, fasteners, sleepers, and roadbed. The adverse effects of vibration can be controlled by reducing the excitation intensity of the vibration source, attenuating vibrations along the propagation path, and isolating vibrations in the foundation and interior of the building. This research method can quickly and accurately predict the vibration and noise conditions of superstructure properties and provide support for vibration and noise reduction in practical engineering.

Recent advancements in immunotherapy have substantially improved overall survival and quality of life among patients with cancer. Notably, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary strategy, particularly in the management of advanced cancers. However, the success of ICIs is accompanied by the challenge of immune-related adverse events. Although rare, cardiovascular adverse events associated with ICIs are associated with high fatality rates and rapid clinical progression, thereby necessitating timely intervention. This review explores the histopathologic characteristics of ICI-induced myocarditis, shedding light on the complexities of diagnosis and management. Several studies examining the histopathologic features of ICI-induced myocarditis have emphasized the roles of macrophages and the potential utility of ancillary tests such as immunohistochemistry. Quantifying CD68+ macrophage abundance may enhance diagnostic sensitivity, thereby providing valuable insights into clinical outcomes. In conclusion, this review underscores the need for a nuanced approach to diagnosing ICI-induced myocarditis. The comprehensive exploration of histopathologic characteristics, ancillary tests, and emerging diagnostic markers provides valuable guidance for practicing pathologists. As the population of ICI-treated patients with cancer continues to grow, optimizing immunohistochemistry panels and refining diagnostic criteria will be crucial to address the unique challenges posed by ICI-induced myocarditis.

Among the most significant solutions suggested for estimating energy consumption and cooling load, one can refer to enhancing energy efficiency in non-residential and residential buildings. A structure's characteristics must be considered when estimating how much heating and cooling is required. To design and develop energy-efficient buildings, it can be helpful to research the characteristics of connected structures, such as the kinds of cooling and heating systems needed to ensure sui interior air quality. As an important part of energy consumption and demand of buildings, the assessment of cooling load conditions from the envelope of large buildings has not been comprehensively understood yet. In the present paper, a new conceptual system has been developed to anticipate cooling load in the sector of residential buildings. Also, the paper briefly describes the major models of the developed system to maintain continuity and concentrate on the prediction model of the cooling load. To predict cooling load, authors have modelled two methods of artificial neural network (ANN) and adaptive neuro-fuzzy inference system (ANFIS) in conjunction with teaching-learning-based optimization (TLBO). This article aims to illustrate how artificial intelligence (AI) approaches play an essential role in addressing the mentioned necessity and help estimate the optimal design parameters for various stations. The value of the multiple determination coefficient is also determined. The values of the training R2 (coefficient of multiple determination) are 0.96446 and 0.97585 for TLBO-MLP and TLBO-ANFIS in the training stage and 0.95855 and 0.9721 in the testing stage, respectively, with an unknown dataset which is acceptable. The training RMSE values for TLBO-MLP and TLBO-ANFIS are 0.0685 and 0.11176 for training and 0.07074 and 0.12035 for testing, respectively, for the unknown dataset, which is acceptable. The lowest RMSE value and the higher R2 value indicate the favourable accuracy of the TLBO-MLP technique. According to the high value of R2 (97%) and the low value of RMSE, TLBO-MLP can predict residential buildings’ cooling load.

Identification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines and immuno-diagnostic reagents, as well as antibody design and production. In this work, we generated a large benchmark dataset comprising 124,879 experimentally supported linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while all sequence-derived and structural features were informative. To search more efficient and interpretive feature representations, a ten-layer deep learning framework for linear BCE prediction, namely NetBCE, was developed. NetBCE achieved high accuracy and robust performance with the average area under the curve (AUC) value of 0.8455 in five-fold cross-validation through automatically learning the informative classification features. NetBCE substantially outperformed the conventional machine learning algorithms and other tools, with more than 22.06% improvement of AUC value compared to other tools using an independent dataset. Through investigating the output of important network modules in NetBCE, epitopes and non-epitopes tended to be presented in distinct regions with efficient feature representation along the network layer hierarchy. The NetBCE is freely available at https://github.com/bsml320/NetBCE.

Modeling, validating, and simulating are three essential parts in investigating the heat mitigation benefits of urban trees (BUT). Therefore, 81 relevant studies from the last ten years are reviewed, analyzed, and summarized in this study. Three main ways for urban trees to adjust the environment are summarized, including shade creation and radiation modification, cooling effects of transpiration, and airflow blocking and modification effects. Research works are analyzed with regard to four categories: (1) heat and moisture exchange mechanisms and their mathematical modeling; (2) verification of modeling predictions based on measurements; (3) thermal performance simulation and prediction; and (4) environmental assessment and human thermal comfort analyses. Future research opportunities are discussed: (1) conduct real-time and in-depth measurements to analyze the mechanisms of heat and moisture transfer of trees in different areas; (2) develop tree radiation attenuation, airflow resistance, and transpiration models to accurately describe heat and moisture transfer processes in the urban environment; and (3) establish a three-dimensional numerical simulation method that can accurately simulate the urban thermal environment with trees. This review provides researchers with an overview and potential research opportunities on the thermal effects of urban trees.

Flame retardant modification of leaf fibers was carried out to solve the technical problem of poor fire resistance of plant fibers and improve the utilization rate of urban fallen leaves in building materials. The modification scheme adopts three flame retardants, i.e., ammonium polyphosphate (APP), magnesium hydroxide (MH), and aluminum hydroxide (ATH), and two covering layers, i.e., pure acrylic polymer lotion and water glass (Na2O · nSiO2) solution. The modified leaf fiber's combustion behavior and pyrolysis properties were tested and analyzed. The physical and mechanical characteristics, as well as the thermal insulation qualities, of leaf fiber cement-based composites (LFCC) were studied at high temperatures. The findings revealed that the three flame retardants had an effect on the chemical structure of leaf fibers. In comparison to leaf fibers without flame-retardant modification, flame-retardant-modified leaf fibers have a much greater thermal stability. and its LOI is greater than 27.0%, which is a fire-retardant material. Except for the sample with water glass as the modified cover layer, at high temperatures, the composite flame-retardant fiber LFCC's mass-loss rate is lower compared with fibers without flame-retardant modification or fibers modified with only one kind of flame-retardant. In the composite flame-retardant modified fiber LFCC, the samples with better strength at high temperature are those with ATH replacing 30% and 50% MH. The thermal conductivity of LFCC is negatively correlated with the range of temperature change.

AimWe sought to evaluate the efficacy of acupuncture in treating the main symptoms of primary Sjögren’s syndrome, specifically dryness, pain, and fatigue.MethodsA total of 120 patients with primary Sjögren’s syndrome were randomized in a parallel-group, controlled trial. Participants received acupuncture or sham acupuncture for the first 8 weeks, then were followed for 16 weeks thereafter. The primary outcome was the proportion of participants with a ≥ 30% reduction in ≥ 2 of 3 numeric analog scale scores for dryness, pain, and fatigue. The secondary outcomes included the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient-reported Index (ESSPRI); the EULAR Sjögren’s Syndrome Disease Activity Index; the Schirmer test score; unstimulated saliva flow; serum immunoglobulin G, A, and M concentrations; the Medical Outcome Study Short Form 36 score; salivary gland ultrasound imaging; and the Hospital Anxiety and Depression Scale score.ResultsThe proportions of patients meeting the primary endpoint were 28.33% (17/60) in the acupuncture group and 31.66% (19/60) in the sham group, without a statistically significant difference (P = 0.705). The IgG concentration at week 16 and the homogeneity in ultrasonography of the salivary glands at week 8 showed significant differences between the 2 groups (P = 0.0490 and P = 0.0334, respectively). No other differences were observed between the 2 groups. ESSPRI and unstimulated saliva flow were improved in both groups compared to baseline, albeit with a significant difference between them.ConclusionIn patients with primary Sjögren’s syndrome, acupuncture did not satisfactorily improve symptoms compared to placebo. However, interesting discoveries and possible underlying reasons were demonstrated and discussed, which may be useful to studies in the future.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02691377].

The concentrations of small microplastics (diameter

Phosphorylation plays an important role in the regulation of molecular circadian clocks. Here the authors utilize multi-omics data from flies to describe the circadian kinome and identify GASKET as a potentially important regulator within the circadian kinase network.

As an important protein acylation modification, lysine succinylation (Ksucc) is involved in diverse biological processes, and participates in human tumorigenesis. Here, we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set, combined 10 types of informative features, and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework. We constructed a new tool named HybridSucc, which achieved area under curve (AUC) values of 0.885 and 0.952 for general and human-specific prediction of Ksucc sites, respectively. In comparison, the accuracy of HybridSucc was 17.84%–50.62% better than that of other existing tools. Using HybridSucc, we conducted a proteome-wide prediction and prioritized 370 cancer mutations that change Ksucc states of 218 important proteins, including PKM2, SHMT2, and IDH2. We not only developed a high-profile tool for predicting Ksucc sites, but also generated useful candidates for further experimental consideration. The online service of HybridSucc can be freely accessed for academic research at http://hybridsucc.biocuckoo.org/.

In eukaryotes, protein phosphorylation is specifically catalyzed by numerous protein kinases (PKs), faithfully orchestrates various biological processes, and reversibly determines cellular dynamics and plasticity. Here we report an updated algorithm of Group-based Prediction System (GPS) 5.0 to improve the performance for predicting kinase-specific phosphorylation sites (p-sites). Two novel methods, position weight determination (PWD) and scoring matrix optimization (SMO), were developed. Compared with other existing tools, GPS 5.0 exhibits a highly competitive accuracy. Besides serine/threonine or tyrosine kinases, GPS 5.0 also supports the prediction of dual-specificity kinase-specific p-sites. In the classical module of GPS 5.0, 617 individual predictors were constructed for predicting p-sites of 479 human PKs. To extend the application of GPS 5.0, a species-specific module was implemented to predict kinase-specific p-sites for 44,795 PKs in 161 eukaryotes. The online service and local packages of GPS 5.0 are freely available for academic research at http://gps.biocuckoo.cn.

The received signal of passive radar based on mobile communication signals contains direct and multipath interference (DMI) signals from multiple co-channel base stations (CCBS). The direct signal spatial spectrum of each CCBS should be obtained first to eliminate the co-channel interference. The performance of the traditional spatial spectrum estimation algorithms based on uniform linear array (ULA) is related to the number of array elements. In the complex co-channel interference environment, the array requires an ultra-large number of array elements and the spatial spectrum estimation resolution is poor. This paper proposes a method for estimating the direct signal spatial spectrum of the CCBS by fusing coprime array and compressive sensing. Firstly, an augmented virtual array signal is constructed by using the second-order statistics of the received signals of the coprime array and then the compressive sensing algorithm is used to estimate the spatial spectrum of the direct signal of the CCBS. The proposed method can achieve higher resolution and higher-degrees-of-freedom (DOFs) performance than traditional ULA by using the same number of array elements. The effectiveness of the proposed method is verified by numerical simulation analysis and experimental data.

Glaciers and glacial lakes in the Bosula Mountain Range need special attention, because their instability may cause disastrous consequences to the downstream settlements and the Sichuan-Tibet Road. The latter is a pivotal traffic line in the Southeast Tibetan Plateau. In order to investigate the state of glaciers and glacial lakes in the Bosula Mountain Range, we estimated the changes in glacier/glacial lake boundaries, glacier surface elevation, and glacier flow velocity between 2000 and 2021 based on multisource remote sensing data. Our results showed that, from the period 2000–2013 to the period 2013–2021, the average shrinking rate of glacier area increased from 0.99 km2/a to 1.74 km2/a, and the average expanding rate of glacial lake area increased from 0.04 km2/a to 0.06 km2/a. From the period 1990–2011 to the period 2015–2019, the average thinning rate of glaciers increased from 0.83 m/a to 1.58 m/a. These results indicate the Bosula Mountain Range is one of the fastest melting glacierized regions in the High Mountain Asia, and the factors that account for this may include quick temperature rise, abundant summer rainfall, and thin debris cover. In spite of strong ice melting, the observed changes in glacier boundaries, surface elevation, and flow velocity show no sign of surge activity, and the frequency of glacier lake outburst has not increased since 1989. Currently, three proglacial lakes that expanded quickly during 2000–2021 are now prominent hazards. They are directly threatened by accidental ice calving and ice avalanche, and their outburst could cause considerable damage to the downstream settlements and the Sichuan-Tibet Road.

Abstract Approximately 15% of human cancers are estimated to be attributed to viruses. Virus sequences can be integrated into the host genome, leading to genomic instability and carcinogenesis. Here, a new deep convolutional neural network (CNN) model is developed with attention architecture, namely DeepVISP, for accurately predicting oncogenic virus integration sites (VISs) in the human genome. Using the curated benchmark integration data of three viruses, hepatitis B virus (HBV), human herpesvirus (HPV), and Epstein‐Barr virus (EBV), DeepVISP achieves high accuracy and robust performance for all three viruses through automatically learning informative features and essential genomic positions only from the DNA sequences. In comparison, DeepVISP outperforms conventional machine learning methods by 8.43–34.33% measured by area under curve (AUC) value enhancement in three viruses. Moreover, DeepVISP can decode cis‐regulatory factors that are potentially involved in virus integration and tumorigenesis, such as HOXB7, IKZF1, and LHX6. These findings are supported by multiple lines of evidence in literature. The clustering analysis of the informative motifs reveales that the representative k‐mers in clusters could help guide virus recognition of the host genes. A user‐friendly web server is developed for predicting putative oncogenic VISs in the human genome using DeepVISP.

In this paper, a new type of unit dew-point evaporative cooler with fibrous membrane was designed and constructed. The effects of three air state parameters (temperature, humidity, air velocity) on the outlet air temperature, wet-bulb efficiency and dew-point efficiency were studied, as well as the regional adaptability in four typical cities in China. The porous fibrous membrane can be used to improve the moisture permeability and diffusion characteristics of the wet channel. It was found that the wicking height rate of the porous fibrous membrane was 0.203 cm/min, the diffusivity rate was 0.118 cm2/s, which was better than the performance of Kraft Paper. The usage of this novel device in Urumqi and Lanzhou, as regions with lower relative humidity, showed better regional adaptability than in Beijing and Shanghai with higher relative humidity. When the inlet air velocity was 1 m/s, the temperature decreased from 33.4 °C to 24.2 °C and 31.3 °C–24.5 °C respectively in the former area, while, decreased from 33.6 °C to 28.1 °C and 34.6 °C–29.5 °C respectively in the latter area. With the inlet air velocity increasing from 1 m/s to 3 m/s, the outlet air temperature would rise, and the wet-bulb efficiency and dew-point efficiency would decrease, but the cooling capacity would increase.

The bone morphogenetic protein (BMP) signaling pathway is highly conserved across many species, and its importance for the patterning of the skeletal system has been demonstrated. A disrupted BMP signaling pathway results in severe skeletal defects. Murine calvaria has been identified to have dual-tissue lineages, namely, the cranial neural-crest cells and the paraxial mesoderm. Modulations of the BMP signaling pathway have been demonstrated to be significant in determining calvarial osteogenic potentials and ossification in vitro and in vivo. More importantly, the BMP signaling pathway plays a role in the maintenance of the homeostasis of the calvarial stem cells, indicating a potential clinic significance in calvarial bone and in expediting regeneration. Following the inherent evidence of BMP signaling in craniofacial biology, we summarize recent discoveries relating to BMP signaling in the development of calvarial structures, functions of the suture stem cells and their niche and regeneration. This review will not only provide a better understanding of BMP signaling in cranial biology, but also exhibit the molecular targets of BMP signaling that possess clinical potential for tissue regeneration.

Various posttranslational modifications (PTMs) participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in human diseases. Therefore, an integral resource of PTM–disease associations (PDAs) would be a great help for both academic research and clinical use. In this work, we reported PTMD, a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of disease-associated PTM events. By reconstructing a disease–gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http://ptmd.biocuckoo.org. Keywords: Posttranslational modification, Phosphorylation, PTM–disease association, Disease–gene network, AKT1

Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15–25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.

A key feature of lung fibrosis is the accumulation of myofibroblasts. Interleukin 13 (IL-13) is a pro-fibrotic mediator that directly and indirectly influences the activation of myofibroblasts. Transforming growth factor beta (TGF-β) promotes the differentiation of fibroblasts into myofibroblasts, and can be regulated by IL-13. However, IL-13's downstream signaling pathways are not completely understood. We previously reported that the transcription factor Yin Yang 1 (YY1) is upregulated in fibroblasts treated with TGF-β and in the lungs of mice and patients with pulmonary fibrosis. Moreover, YY1 directly regulates collagen and alpha smooth muscle actin (α-SMA) expression in fibroblasts. However, it is not known if IL-13 regulates fibroblast activation through YY1 expression. We hypothesize that IL-13 up-regulates YY1 expression through regulation of AKT activation, leading to fibroblast activation. In this study we found that YY1 was upregulated by IL-13 in lung fibroblasts in a dose- and time-dependent manner, resulting in increased α-SMA. Conversely, knockdown of YY1 blocked IL-13-induced α-SMA expression in fibroblasts. Furthermore, AKT phosphorylation was increased in fibroblasts treated with IL-13, and AKT overexpression upregulated YY1, whereas blockade of AKT phosphorylation suppressed the induction of YY1 by IL-13 in vitro. In vivo YY1 was upregulated in fibrotic lungs from CC10-IL-13 transgenic mice compared to that from wild-type littermates, which was associated with increased AKT phosphorylation. Taken together, these findings demonstrate that IL-13 is a potent stimulator and activator of fibroblasts, at least in part, through AKT-mediated YY1 activation.

Abstract These multimedia modules have been developed to teach senior medical students on their surgical pathology elective the basic microscopic features of common surgical pathology diagnoses. The modules include normal histology and pathology organized into the following organ systems: breast, gastrointestinal, genitourinary, gynecologic, liver, and lung. The first component to this teaching set is a review of normal histology which may serve as a comparison for the histopathology component. A low- and high-power micrograph of each organ is provided. The student is tested with a quiz of micrographs of normal histology where they must identify the organ. Next, students review commonly encountered biopsies in each organ system. Under each diagnosis is listed the definition, etiology, symptoms/indications for biopsy, gross features, microscopic features, and a differential diagnosis. Radiologic features and pertinent additional stains are noted when appropriate. The goal of the surgical pathology rotation at this institution is to allow students to function as junior house officers, actively participating in previewing and sign-out. These teaching modules will provide basic clinical and microscopic descriptions to help the student preview and diagnose biopsy specimens on their own. The clinical implications of certain diagnoses as they pertain to aggressive management in neoplastic disease will also be mentioned. The modules are designed so students can easily navigate between slides, diagnoses, and differentials. Each image is provided with arrows and labels (which may be hidden) to guide the eye of the learner to recognize the patterns of each diagnosis. After completing a module, students will solidify their knowledge with a quiz. We plan to monitor the effectiveness of this assessment by having students take the quiz at the start and end of the rotation to compare the change in their score. These modules will provide an organized foundation on which the student may build his or her knowledge during slide review with senior residents or staff pathologists.

Non-typeable Haemophilus influenza (NTHi) is an important human pathogen causing respiratory tract infections in both adults and children. NTHi infections are characterized by inflammation, which is mainly mediated by nuclear transcription factor kappaB (NF-kappaB)-dependent production of inflammatory mediators. The deubiquitinating enzyme cylindromatosis (CYLD), loss of which was originally reported to cause a benign human syndrome called cylindromatosis, has been identified as a key negative regulator for NF-kappaB in vitro. However, little is known about the role of CYLD in bacteria-induced inflammation in vivo. Here, we provided direct evidence for the negative role of CYLD in NTHi-induced inflammation of the mice in vivo. Our data demonstrated that CYLD is induced by NTHi in the middle ear and lung of mice. NTHi-induced CYLD, in turn, negatively regulates NTHi-induced NF-kappaB activation through deubiquitinating TRAF6 and 7 and down-regulates inflammation. Our data thus indicate that CYLD acts as a negative regulator for NF-kappaB-dependent inflammation in vivo, hence protecting the host against detrimental inflammatory response to NTHi infection.

A compact spoof surface plasmon polariton (SSPP) low-pass filter is proposed. By adopting a novel fishbone structure, the effective depth of the groove is increased, reducing the filter width by 24.84%. The length of the filter is reduced by 22.23% with a new transmission structure. To intuitively display this structure, the filter is designed and fabricated. The area of the filter is 47.44 mm×8 mm. The results demonstrate that the insertion and return losses are less than 3 dB and greater than 13 dB, respectively, in a wideband range of 0-10.00 GHz. [ABSTRACT FROM AUTHOR]

Among the most significant solutions suggested for estimating energy consumption and cooling load, one can refer to enhancing energy efficiency in non-residential and residential buildings. A structure's characteristics must be considered when estimating how much heating and cooling is required. To design and develop energy-efficient buildings, it can be helpful to research the characteristics of connected structures, such as the kinds of cooling and heating systems needed to ensure sui interior air quality. As an important part of energy consumption and demand of buildings, the assessment of cooling load conditions from the envelope of large buildings has not been comprehensively understood yet. In the present paper, a new conceptual system has been developed to anticipate cooling load in the sector of residential buildings. Also, the paper briefly describes the major models of the developed system to maintain continuity and concentrate on the prediction model of the cooling load. To predict cooling load, authors have modelled two methods of artificial neural network (ANN) and adaptive neuro-fuzzy inference system (ANFIS) in conjunction with teaching-learning-based optimization (TLBO). This article aims to illustrate how artificial intelligence (AI) approaches play an essential role in addressing the mentioned necessity and help estimate the optimal design parameters for various stations. The value of the multiple determination coefficient is also determined. The values of the training R² (coefficient of multiple determination) are 0.96446 and 0.97585 for TLBO-MLP and TLBO-ANFIS in the training stage and 0.95855 and 0.9721 in the testing stage, respectively, with an unknown dataset which is acceptable. The training RMSE values for TLBO-MLP and TLBO-ANFIS are 0.0685 and 0.11176 for training and 0.07074 and 0.12035 for testing, respectively, for the unknown dataset, which is acceptable. The lowest RMSE value and the higher R² value indicate the favourable accuracy of the TLBO-MLP technique. According to the high value of R² (97%) and the low value of RMSE, TLBO-MLP can predict residential buildings' cooling load. [ABSTRACT FROM AUTHOR]

Patients who have received haematopoietic stem cell transplantation (HSCT) have a high rate of pulmonary complications, and in this immunosuppressed population, fungal pneumonia is of great concern. Fungal pneumonia can have a similar appearance to non-infectious pulmonary processes in HSCT patients, and radiologists should be familiar with the subtle features that may help to differentiate these disease entities. The focus of this article is on the diagnosis of fungal pneumonia in HSCT patients with an emphasis on radiologists’ roles in establishing the diagnosis of fungal pneumonia and the guidance of clinical management. [ABSTRACT FROM AUTHOR]

The article describes the case of a 51-year-old female with recurrent nonspecific interstitial pneumonia of the fibrotic pattern (NSIP-F) in the lung allograft and manifested de novo clinical and serological features of antisynthetase syndrome after bilateral lung transplantation for advanced idiopathic fibrotic NSIP. Topics discussed include progressive pulmonary fibrosis, connective tissue disease-associated interstitial lung disease, and treatment with hydroxychloroquine and rituximab.

Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma. [ABSTRACT FROM AUTHOR]

Background--How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. Methods and Results--We investigated canonical Wnt/ß-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin-related cardiomyopathy. Our data demonstrated that canonical Wnt/β-catenin signaling was activated through nuclear accumulation of β-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin-related cardiomyopathy when compared with nonfailing controls and transcription factor 7-like 2 (TCF7L2) was the main β-catenin partner of the T-cell factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that β-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that β-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes. Conclusions--This study indicates that TCF7L2 mediates canonic Wnt/β-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt/β-catenin to c-Myc axis can be explored for preventing and treating heart failure. [ABSTRACT FROM AUTHOR]

Primary ovarian carcinoids and metastatic tumors share similar morphologic features. Metastatic carcinoids must be excluded from primary ones for prognostic and therapeutic reasons. Gastrointestinal neuroendocrine (carcinoid) tumors are much more common with the majority arising from small intestine and appendix. The aim of this study is to evaluate the role of immunohistochemistry for CDX2 in differentiating primary ovarian from metastatic carcinoids of primary gastrointestinal origin. Thirty primary pure ovarian carcinoids, 16 primary ovarian carcinoids arising in association with benign teratomas, 10 ovarian carcinoids metastatic from primary gastrointestinal tract and 70 gastrointestinal neuroendocrine tumors were studied for the expression of CDX2 by immunohistochemistry. CDX2 expression revealed that 40 (57.1%) of 70 cases of gastrointestinal carcinoids and 9 (90%) of 10 ovarian metastatic carcinoids showed positive nuclear staining (diffuse or focal). On the other hand, 3 (18.8%) of 16 primary carcinoids with teratomatous elements showed weak positivity. Among the 70 gastrointestinal carcinoids, CDX2 was positive in 38 (90.5%) of 42 cases in the duodenum, small intestine, appendix, and only in 2 (11.8%) of 17 cases of colorectal carcinoids and none of the 11 cases in the stomach. It is concluded that CDX2 may be a useful marker to distinguish primary ovarian carcinoid from metastasis from small intestinal and appendiceal neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

Mutation analysis of epidermal growth factor receptor (EGFR) is essential in determining the therapeutic strategy for lung adenocarcinoma. Immunohistochemical (IHC) staining with EGFR mutation--specific antibodies of del E746-A750 in exon 19 and L858R in exon 21 has been evaluated in resection specimens in a few studies but rarely in biopsy samples. A total of 169 cases (78 biopsies and 91 resected specimens) of lung adenocarcinoma with EGFR mutation status predefined by direct DNA sequencing were histologically examined, and IHC was performed using EGFR mutation--specific antibodies of del E746-A750 and L858R. The cases with positive results by IHC but negative results by direct DNA sequencing were examined by amplified refractory mutation system. Our results showed that the frequency of EGFR mutations for both E746-A750 deletion and L858R mutation was 38.5% (65/169) by DNA sequencing or amplified refractory mutation system and 34.3% (58/169) by IHC in lung adenocarcinomas. Based on molecular test results, the overall sensitivity, specificity, positive predictive value, and negative predictive value of IHC using these 2 antibodies in all (biopsy/resection) cases were 87.7% (80%/94.3%), 99.0% (97.9%/100%), 98.3% (96%/100%), and 92.8% (88.7%/96.6%), respectively. Lung adenocarcinomas with a predominant acinar, papillary, lepidic, or solid growth pattern more often harbor EGFR mutation of del E746-A750 or L858R. In conclusion, the immunostaining with EGFR del E746-A750 and L858R mutation antibodies is a reliable screening method with high specificity and sensitivity for identifying the EGFR mutation in both resected and biopsied lung adenocarcinomas. [ABSTRACT FROM AUTHOR]

Background: The recent development of antibodies specific for the major hotspot mutations in the epidermal growth factor receptor (EGFR), L858R and E746_A750del, may provide an opportunity to use immunohistochemistry (IHC) as a screening test for EGFR gene mutations. This study was designed to optimize the IHC protocol and the criteria for interpretation of the results using DNA sequencing as the gold-standard. Methods: Tumor sections from fifty lung adenocarcinoma specimens from Chinese patients were immunostained using L858R and E746_A750del-specific antibodies using three different antigen retrieval solutions, and the results were evaluated using three different sets of criteria. The same specimens were used for DNA purification and analysis of EGFR gene mutations. Results: In this study the optimal buffer for antigen retrieval was EDTA (pH 8.0), and the optimal scoring method was to call positive results when there was moderate to strong staining of membrane and/or cytoplasm in >10% of the tumor cells. Using the optimized protocol, L858R-specific IHC showed a sensitivity of 81% and a specificity of 97%, and E746_A750del-specific IHC showed a sensitivity of 59% and a specificity of 100%, both compared with direct DNA analysis. Additionally, the mutant proteins as assessed by IHC showed a more homogeneous than heterogeneous pattern of expression. Conclusions: Our data demonstrate that mutation-specific IHC, using optimized procedures, is a reliable prescreening test for detecting EGFR mutations in lung adenocarcinoma. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2059012601872392 [ABSTRACT FROM AUTHOR]

NaV1.5 is a cardiac voltage-gated Na+ channel αsubunit and is encoded by the SCN5a gene. The activity of this channel determines cardiac depolarization and electrical conduction. Channel defects, including mutations and decrease of channel protein levels, have been linked to the development of cardiac arrhythmias. The molecular mechanisms underlying the regulation of NaV1.5 expression are largely unknown. Forkhead box O (Foxo) proteins are transcriptional factors that bind the consensus DNA sequences in their target gene promoters and regulate the expression of these genes. Comparative analysis revealed conserved DNA sequences, 5'-CAAAACA-3' (insulin responsive element, IRE), in rat, mouse and human SCN5a promoters with the latter two containing two overlapping Foxo protein binding IREs, 5'-CAAAACAAAACA-3'. This finding led us to hypothesize that Foxo1 regulates NaV1.5 expression by directly binding the SCN5a promoter and affecting its transcriptional activity. In the present study, we determined whether Foxo1 regulates NaV1.5 expression at the transcriptional level and also defined the role of Foxo1 in hydrogen peroxide (H2O2)-mediated NaV1.5 suppression in HL-1 cardiomyocytes using chromatin immunoprecipitation (ChIP), constitutively nuclear Foxo1 expression, and RNAi Foxo1 knockdown as well as whole cell voltage-clamp recordings. ChIP with anti-Foxo1 antibody and follow-up semi-quantitative PCR with primers flanking Foxo1 binding sites in the proximal SCN5a promoter region clearly demonstrated enrichment of DNA, confirming Foxo1 recruitment to this consensus sequence. Foxo1 mutant (T24A/S319A-GFP, Foxo1-AA-GFP) was retained in nuclei, leading to a decrease of NaV1.5 expression and Na+ current, while silencing of Foxo1 expression by RNAi resulted in the augmentation of NaV1.5 expression. H2O2 significantly reduced NaV1.5 expression by promoting Foxo1 nuclear localization and this reduction was prevented by RNAi silencing Foxo1 expression. These studies indicate that Foxo1 negatively regulates NaV1.5 expression in cardiomyocytes and reactive oxygen species suppress NaV1.5 expression through Foxo1. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 76-year-old man with known metastatic papillary thyroid carcinoma who presented with progressive cough and dyspnea on exertion over a four-month period. The medical history of the patient is detailed. It offers information on the treatments administered to the patient. The clinical features and pathology of thyroid carcinoma are discussed.

Background: Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growth factor mRNA-binding protein family, is expressed in several human malignancies, including melanomas. However, the expression of IMP-3 has not been explored in melanoma in situ, various histologic subtypes of invasive melanomas and atypical Spitz tumors. Methods: IMP-3 immunostain was performed in 157 melanocytic lesions. Results: Nearly all benign (8/8), dysplastic (8/8) and Spitz nevi (8/9) were negative for IMP-3. Focal IMP-3 positivity was observed in 5/12 melanoma in situ and 4/15 superficial melanomas (Breslow depth ≤1 mm). Half (10/20) of deep melanomas (Breslow depth >1 mm) and 25/52 metastatic melanomas demonstrated strong IMP-3 staining. IMP-3 expression differs significantly between non-desmoplastic melanomas (superficial and deep) and benign or dysplastic or Spitz nevi (p = 0.0427, respectively). Four of 23 desmoplastic melanomas expressed IMP-3 , which was significantly different from deep melanomas (p = 0.0109). IMP-3 stained 7 of 10 atypical Spitz tumors. The difference between atypical Spitz tumors and Spitz nevi was statistically significant (p = 0.0256). Conclusion: A malignant circumstance, such as non-desmoplastic melanoma or atypical Spitz tumor, can be inferred when IMP-3 is expressed, suggesting potential diagnostic value of IMP-3 in melanocytic lesions. Yu L, Xu H, Wasco MJ, Bourne PA, Ma L. IMP-3 expression in melanocytic lesions. [ABSTRACT FROM AUTHOR]

The article discusses the study which aims to examine the role of cyclic nucleotide phosphodiesterases (PDE1) in balancing intracellular cardiomyocyte hypertrophy and cyclic guanosine monophosphate (cGMP). In the process, PDE1A used small interfering RNA to neonatal and adult rat ventricular myocytes in determining the chronic isoproterenol infusion in vivo in human hearts. Thus, PDE1A reduced the intracellular cGMP and cGMP-dependent protein kinase towards cardiomyocyte hypertrophy.

The article presents a study on the role of reactive oxygen species-induced activation of p90 ribosomal S6 kinase (p90RSK) in cardiac repolarization. It mentions arrhythmias, hydrogen peroxide, phosphorylation, and currents to expound on the study. This study suggests that p90RSK prolongs cardiac repolarization through the inhibition of outward K+ channel activity.

Background: Immunohistochemistry is helpful in distinguishing metastatic carcinoma from atypical mesothelial cells; however, it is not useful in differentiating atypical mesothelial cells from malignant mesothelial cells. K homolog domain containing protein overexpressed in cancer (KOC), a member of the insulin-like growth factor mRNA-binding protein (IMP) family, also known as L523S and IMP3, is expressed during embryogenesis and in various malignancies. Using a mouse monoclonal antibody (L523S) against KOC, KOC expression was investigated in malignant tumors and reactive mesothelial cells in serous effusions.Methods: Seventy-six cases with paraffin-embedded pleural, pericardial, and peritoneal serous effusion cell blocks including 60 malignant serous effusions (11 malignant pleural mesotheliomas and 49 metastatic carcinomas) and benign pleural effusions (14 cases with reactive mesothelial cells and 2 cases with atypical cells with uncertain significance) were selected for immunohistochemical analysis with L523S, calretinin, and CK5/6.Results: Immunohistochemical studies showed that positive staining for KOC of variable degrees of intensity was observed in 47 of 60 cases in malignant serous effusions including 10 of 11 mesotheliomas and 36 of 49 metastatic carcinomas. The associated reactive mesothelial cells were negative for KOC but positive for calretinin and CK5/6. All 11 malignant mesotheliomas exhibited positivity for calretinin, and 9 of 11 cases had CK5/6 staining. In addition, 16 cases that were originally diagnosed either as pleural effusions with reactive mesothelial cells (14) or atypical cells with uncertain significance (2) were also tested for KOC expression. Interestingly, 3 of 16 cases exhibited various degrees of positivity for KOC, 2 of which were diagnosed as lung adenocarcinoma with a recurrence after tumor resection and 1 as malignant pleural mesothelioma.Conclusions: Anti-L523S antibody is a useful marker for the detection of malignant cells in serous effusions and it can have significant utility in differentiating reactive mesothelial cells from malignant mesothelioma and metastatic carcinoma in combination with calretinin and CK5/6 staining. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumor (SFT) is an unusual meserichymal neoplasm that most often arises in the pleura; however, it has recently been described in a number of extrapleural sites. This report describes an extremely rare case of a benign SET arising in the pancreas. A 41- year-old woman presented in the clinic with right upper abdominal pain. Subsequent ultrasonographic studies revealed a 1.5 x 1.5 x 1.4 cm hypoechoic mass within the pancreatic body, which was later confirmed on both helical computerized tomography and magnetic resonance imaging studies. An endocrine tumor was clinically suspected. Laparoscopic enucleation of the mass was performed. Microscopically, the tumor was composed of bland uniform spindle cells arranged between collagen bundles. On immutiohistochemical studies, these spindle cells were positive for CD34 and bcl-2 but negative for cytokeratin (AE1+AE3 and Cam5.2), smooth muscle actin, desmin, S-100, and c-kit. Based on the light microscopic morphology and immunohistochemical staining profile, the diagnosis of SFT was rendered. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) family members are multifunctional growth factors involved in regulating diverse biological processes. Despite the critical role for TGF-β in regulating cell proliferation, differentiation, migration and development, its role in regulating NF-κB-dependent inflammatory response still remains unclear. Here, we show that TGF-β1 induces acetylation of NF-κB p65 subunit to synergistically enhance bacterium nontypeable Haemophilus influenzae-induced NF-κB activation and inflammatory response in vitro and in vivo. The TGF-β1-induced acetylation of p65 is mediated via a Smad3/4-PKA-p300-dependent signaling pathway. Acetylation of p65 at lysine 221 by TGF-β1 is critical for synergistic enhancement of bacteria-induced DNA-binding activity, NF-κB activation, NF-κB-dependent transcription of TNF-α and IL-1β and interstitial polymorphonuclear neutrophil infiltration in vitro and in vivo. These studies provide new insights into the novel regulation of NF-κB by TGF-β signaling. [ABSTRACT FROM AUTHOR]