Gastric cancer has become a global health issue, severely disrupting daily life. Early detection in gastric cancer patients and immediate treatment contribute significantly to the protection of human health. However, routine gastric cancer examinations carry the risk of complications and are time-consuming. We proposed a framework to predict gastric cancer non-invasively and conveniently. A total of 703 tongue images were acquired using a bespoke tongue image capture instrument, then a dataset containing subjects with and without gastric cancer was created. As the images acquired by this instrument contain non-tongue areas, the Deeplabv3+ network was applied for tongue segmentation to reduce the interference in feature extraction. Nine tongue features were extracted, relationships between tongue features and gastric cancer were explored by using statistical methods and deep learning, finally a prediction framework for gastric cancer was designed. The experimental results showed that the proposed framework had a strong detection ability, with an accuracy of 93.6%. The gastric cancer prediction framework created by combining statistical methods and deep learning proposes a scheme for exploring the relationships between gastric cancer and tongue features. This framework contributes to the effective early diagnosis of patients with gastric cancer. Gastric cancer is one of the most prevalent malignancies in humans, and the reason for many deaths each year . Early-sThe most commonly used method for the detection of gastric cancer is gastroscopy . By obseTongue diagnosis is a non-invasive diagnostic modality to diagnose the status of patients conveniently. Tongue features not only reveal the physical condition of the organs but also correlate with their functions . SignifiRecently, instead of observing and recording tongue features, research has been focusing on objective tongue feature analysis with the benefit of modern technology. Tongue features have been digitally analyzed to discover convenient ways to detect diseases ,11,12. TStudies exploring the links between gastric cancer and tongue features have contributed to the detection of gastric cancer. Gastric cancer has been confirmed to be correlated with microbiota in the oral cavity, such as helicobacter pylori ,20. The The main contribution and innovation of this study is to investigate the feasibility of predicting gastric cancer by the tongue. Because no open-source dataset of gastric cancer tongue images exists, a tongue image capture instrument was used to acquire tongue images of gastric cancer subjects and non-gastric cancer subjects. Based on image pre-processing and image enhancement, an original dataset was constructed. Next, the image segmentation algorithm was used for the tongue segmentation task. Then, nine tongue features were extracted with guidance from professional physicians. The association between these tongue features and gastric cancer is explored by using differential analysis, importance analysis and correlation analysis. Four tongue features that contribute to the prediction of gastric cancer are screened and retained. These four features including tongue shape, saliva, tongue coating thickness and tongue coating texture are used as a basis for predicting gastric cancer. Finally, a framework using EfficientNet  is estabGastric cancer is an enormous threat to human health. Early detection of gastric cancer has a positive significance in reducing the mortality rate of gastric cancer patients. As one of the effective methods to diagnose gastric cancer, the physician can visually observe the changes of gastric mucosa and the size of the lesions. However, the detection results are affected by the work experience and subjective perception of physicians. To overcome these limitations, researchers ,26,27 buJiang et al.  construcTherefore, we extracted nine tongue features and explored the relationship between them and gastric cancer. Through differential analysis, importance analysis, and correlation analysis, tongue shape, saliva, tongue coating thickness and tongue coating texture were finally selected as the input features for predicting gastric cancer. In addition, we used image segmentation to remove non-tongue regions before building the gastric cancer prediction framework to reduce interference and improve the efficiency and accuracy of prediction.To ensure the established framework had clinical application, we used an instrument to collect the tongue images of gastric cancer patients and non-gastric cancer subjects in hospitals. The images captured by the tongue image acquisition instrument contain non-tongue areas such as the face and the instrument. Non-tongue regions are significantly reduced by image pre-processing, which is helpful to improve the efficiency of image segmentation. The processed tongue images were input into the gastric cancer prediction framework, then the final prediction results were obtained.Data was collected from Shanxi Cancer Hospital and the Affiliated Hospital of Shanxi University of Traditional Chinese Medicine from January 2021 to August 2022, with 703 images in total. The dataset consisted of 103 tongue images of gastric cancer patients and 600 tongue images of non-gastric cancer subjects that included patients with other diseases and normal individuals. The diseases of these subjects were definitely diagnosed. Tongue images of the patient were captured under the guidance of specialized physicians. The subjects were arranged to sit in front of the instrument and extend their tongue naturally . During The resolution of the acquired tongue image was 3264 × 2488 with horizontal and vertical resolution of 96 dpi. High-resolution tongue images containing non-tongue regions consume a lot of computational resources in the deep learning network. The tongue region extraction method proposed by Li  was emplIn addition to the tongue region, images acquired by the tongue image capture instrument frequently contained areas, such as lips and teeth. The tongue-part of the images was segmented to eliminate the influence of non-tongue areas on the subsequent analysis. Existing automatic tongue segmentation approaches are classified into two categories, namely segmentation models based on traditional methods, such as the region growing method and the thresholding method, and segmentation networks based on deep learning. Traditional segmentation methods are insensitive to the color of the regions close to the tongue and easily mistake these regions for the tongue ,37,38. IThe Deeplabv3+ network is based on an encoder-decoder architecture. The encoder part consists of a network for extracting features and multiple parallelly dilated convolution layers. The MobileNetV2  is used −2. In the last 100 epochs of unfrozen training, the learning rate of the global network was 1 × 10−4.The data set used for tongue segmentation was divided in a 7:2:1 ratio into the training set, validation set and test set. The MobileNetV2 network weight trained on ImageNet was used as the beginning weight. The Adam optimizer  was usedTongue shape: fat tongue, thin tongue and normal tongue;Tooth-marked tongue: tooth mark and normal;Spots and prickles tongue: Spots and prickles and normal;Saliva: dry and normal;Tongue coating thickness: thick and thin;Tongue coating texture: greasy and normal;Tongue color: pale white, pale red, red and deep red;Tongue coating color: white and yellow;Tongue Fissure: fissured tongue and normal.Combining the professional opinions of several doctors, nine tongue features were extracted to explore the difference between the tongues of gastric cancer patients and non-gastric cancer subjects. The extracted tongue features are listed in the following paragraphs.The differences in tongue features between the gastric cancer patients and the control group were contrasted using statistical methods. The cross-plot of tongue features between the two groups is shown in p-value < 0.001). Statistics were based on the p-value obtained by the significance test method, with p-value < 0.001 considered as a highly significant difference, 0.001 < p-value < 0.005 considered as a significant difference, and p-value > 0.005 considered as no significant difference.The tongue features of the two groups were contrasted using chi-square test and independent t-tests to explore features that were significantly different . The proportion of yellow tongue coating in gastric cancer patients was significantly higher than in the control group . In addition, the proportion of spots and prickles tongue in gastric cancer patients was significantly higher than in the control group . No significant difference was detected between patients with gastric cancer and the control group in tongue color and tongue fissure .The differences in tongue features between patients with gastric cancer and the control group are shown in The XGBT algorithm  was utilSubsequently, the association between the nine tongue features of the gastric cancer patients was explored. Correlation analysis was applied to analyze two or more features that were correlated to measure the closeness of the correlation. The correlations between the tongue features of gastric cancer patients are shown in Utilizing statistical methods and artificial intelligence techniques for tongue feature analysis, the tongue features with significant differences, high importance scores and high correlations between the gastric cancer patients and the control group were selected as input features for the gastric cancer prediction framework. Finally, tongue shape, saliva, tongue coating thickness and tongue coating texture were also used as features to build a deep learning gastric cancer prediction framework.To avoid the shortcomings of single feature scale, easy saturation of dimensional scaling and poor classification effect in traditional image classification algorithms, the EfficientNet network was used to classify gastric cancer and non-gastric cancer tongue images. Compared with different CNN models, the EfficientNet model successfully achieved a higher accuracy and efficiency. It used a simple and efficient composite coefficient to scale the network in three dimensions: network depth, network width and image resolution. The MBConv block in MobileNetV2 was used as the backbone of the EfficientNet network. The MBConv block was composed of two convolutional layers, a depth-separable convolutional layer, and a feature extraction module. The basic network architecture of EfficientNet-B0 is shown in −4. At the end of the framework, the Softmax classifier normalized the two classification results and the output values were transformed into probabilities. In the final output layer, the output value with the highest probability was selected as the predicted result.The dataset used to build the prediction framework was divided in an 8:1:1 ratio into the training set, validation set and test set. When the EfficientNet network model was trained on the dataset, the official weight was used as the initial weight of the model. After 200 epochs, the training ended with a learning rate of 1 × 10The experiments were performed on a Windows 10 operating system, Intel Core i7-10700, NVIDIA GeForce RTX 2060, based on Pytorch deep learning framework.In this section, the effectiveness of the segmentation method and gastric cancer prediction framework was assessed with four metrics. The performance of the Deeplabv3+ network was evaluated using the mean intersection over union (MIou) and mean pixel accuracy (MPA) . Accurack is the number of categories in the image except the background, iip is the number of pixels belonging to category i that are predicted to be in category i, ijp is the number of pixels belonging to category i that are predicted to be in category j.MIou is the standard evaluation method for segmentation methods. The specific value of the intersection of the predicted segmentation and ground truth of each class of pixels to the union set is calculated. The ratios of all classes are then summed and averaged to obtain MIou:MPA is based on pixel accuracy (PA). The specific value of the number of pixels correctly predicted in each class to the total number of pixels was calculated to obtain the PA. The PAs of all classes were then summed and averaged to obtain the MPA:Accuracy is the proportion of samples correctly predicted by the model to the total sample:The F1-score is a performance evaluation index of a binary classification model. It is a balance between the precision and recall giving a more balanced metric by calculating the harmonic mean of precision and recall:To validate the segmentation effect of the Deeplabv3+ network, other models commonly used for medical image segmentation were built for comparison with the Deeplabv3+ network. The segmentation networks were evaluated with MIou and MPA. The segmentation effect of the three networks evaluated is shown in The validity of the gastric cancer prediction framework was tested on a validation set containing tongue images of gastric cancer patients and tongue images without non-gastric cancer. Seventy tongue images in the dataset were used to test the effectiveness of the framework. Representative samples of the tongue images in the test set are shown in The tongue images of gastric cancer patients and the control group in the validation set were input into the framework to assess its prediction effect. The accuracy of the framework was 93.6%, and the F1-score was 92.6%. A gastric cancer prediction framework was built by statistical analysis of tongue features and deep learning. The framework has high accuracy in detecting gastric cancer patients and the detection process has the advantage of being non-invasive. This study presents a novel approach to exploring the relationship between gastric cancer and tongue features, which has clinical application.The presented framework has a strong detection ability, but two aspects can be continuously improved. A major part of the time was spent collecting the images in hospitals, but the number of tongue images collected from gastric cancer patients was still low, which is a common problem in the area of medical image studies. Second, tongue images were collected using a standard capture instrument, but the tongue extension posture of each patient has an impact on subsequent tongue feature extraction.Cancer is a major public health problem worldwide. The penetration of artificial intelligence technology into the medical field has become more convenient and accurate to detect gastric cancer. In this paper, we proposed a prediction framework for gastric cancer based on tongue features and deep learning. The framework predicts gastric cancer patients non-invasively and conveniently. Tongue images are acquired by using a standard tongue image capture instrument, and the Deeplabv3+ network is applied to accurately segment the tongue region. Nine tongue features are extracted with guidance from professional doctors, and the relationships between tongue features and gastric cancer are explored by using statistical methods and deep learning. Through differential analysis, importance analysis, and correlation analysis, tongue shape, saliva, tongue coating thickness and tongue coating texture were finally selected as the input features for predicting gastric cancer. Finally, the EfficientNet network was used to build a gastric cancer prediction framework. The experimental results showed that this framework could accurately distinguish between gastric cancer patients and non-gastric cancer subjects with an accuracy of 93.6%. Compared to other similar work, our framework incorporates more tongue features and can more comprehensively predict gastric cancer.Future work will focus on acquiring more tongue images of gastric cancer patients to extract and further analyze tongue features. Meanwhile, we should improve the framework structure and enhance the robustness of the framework to obtain more accurate gastric cancer prediction results.


Collar-button abscesses are deep space infections of the hand.We present a case of a 66-year-old man who developed an acute collar-button abscess of the hand after a concrete bench fell onto the dorsal aspect of his hand. The hand abscess was managed successfully with intravenous antibiotics and operative intervention.While such infections comprise a small percentage of hand infections, insufficient or delayed treatment results in permanent hand disfiguration and dysfunction. This case highlights an uncommon dorsal-to-volar pattern of hand abscess extension.Knowledge of the anatomy of the hand is essential to diagnosis and appropriate surgical management. •We present a collar-button hand abscess that began as a dorsal web space infection with quick invasion into the volar space.•Collar button abscesses may mimic the presentation of cellulitis and suppurative tenosynovitis.•Diabetic hand infections are poorly understood and recognized, often resulting in delayed diagnosis and severe morbidity. The incidence of deep space hand infections is higher in patients with poorly controlled diabetes Staphylococcus aureus and group A Streptococcus, with S. aureus reported to be present in 80 % cultures The most common infectious agents are We present an unusual case of an aggressive collar-button hand abscess that began as an infection of the dorsal web space with later invasion into volar space. We achieved a favorable resolution with aggressive surgical treatment. This case highlights the importance of early detection and expedited treatment since clinical presentation is often overlooked until serious consequences occur.This work has been reported in line with the SCARE 2020 criteria 29/L. Radiographs of the hand revealed soft tissue swelling in entire right palm, extending to the distal interphalangeal joints of the third and fourth digits with intact bony anatomy, without fractures or dislocations  and microangiopathy of the distal extremities Collar button abscess may present similarly to cellulitis and suppurative infections. Our patient's condition was initially misdiagnosed as cellulitis and fourth digit tenosynovitis. Flexor tendon sheath infections are devastating and are clinically recognized by Kanavel's four cardinal signs: tenderness along the course of the flexor tendon sheath, semiflexed digit positioning, pain with passive extension of the digit, and symmetric swelling of the entire digit Proper decompression of a collar button abscess always requires volar and dorsal incisions because of the communicating channel between the volar and dorsal hand 4This patient had a bruise on the dorsal aspect of the hand, which we hypothesize to have become infected and involve deeper fascial spaces. This case is unique in that the abscess propagated by dorsal to palmar spread. Collar button abscesses usually result from contiguous spread dorsally, most often from an infected palmar injury. A high index of suspicion coupled with excellent knowledge of hand anatomy and function allows for accurate diagnosis and effective management. It is important to diagnose collar-button abscess early as it guides the decision to make two incisions, one on dorsal and another on volar aspect of the hand, to avoid incomplete evacuation of abscess and reoperation. Delay in treatment could result in the spread of infection throughout the deep spaces, risking significant compromise of hand function and damage to neurovascular structures.N/A.Not commissioned, externally peer-reviewed.None.Not applicable.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editorin-Chief of this journal on request.JA and DH were equally involved in the writing of the manuscript. SP was involved in the editing/supervision of the manuscript.We would like to acknowledge Dr. Antonio Alvarez-Mendoza for his insights, guidance and expertise with the pathological specimens from this case.N/A.Savvas Poulos MD.All authors declare no conflicts of interest.


Then, we present evidence of dopaminergic modulation of synaptic plasticity in the hippocampus. Plasticity mechanisms are examined in brain slices and in recordings from in vivo neuronal populations in freely moving rodents. Finally, we review pharmacological, genetic, and circuitry research that demonstrates the importance of dopamine release for learning and memory tasks while dissociating anatomically distinct populations of direct dopaminergic inputs.The hippocampus is responsible for encoding behavioral episodes into short-term and long-term memory. The circuits that mediate these processes are subject to neuromodulation, which involves regulation of synaptic plasticity and local neuronal excitability. In this review, we present evidence to demonstrate the influence of dopaminergic neuromodulation on hippocampus-dependent memory, and we address the controversy surrounding the source of dopamine innervation. First, we summarize historical and recent retrograde and anterograde anatomical tracing studies of direct dopaminergic projections from the ventral tegmental area and discuss dopamine release from the adrenergic  The low extracellular concentrations of DA in the hippocampal formation, especially in comparison to the striatum, have initially led scientists to believe that the hippocampus was completely devoid of DA innervation  into the dorsal hippocampus. This selective monoaminergic toxin caused destruction of midbrain DA afferents, producing a dramatic decrease in DA content in the dorsal hippocampus  and stratum radiatum (SR) in agreement with what was previously shown with ChR2 expression. These labeled puncta and fibers were also immuno-positive for TH, confirming their midbrain dopaminergic identity.To address the source of DA innervation, two recent studies used a sensitive anterograde viral tracing methodology to examine the distribution of direct midbrain dopaminergic projections to the dCA1 , which is the source of noradrenergic input to the dorsal hippocampus. The procedure leaves midbrain dopaminergic fibers and terminals as the sole source of the TH signal in the hippocampus. TH immunofluorescence was significantly reduced in the dCA1 region of THLC KO mice, particularly in the SO and SR, but a substantial signal remained in the PCL. The remaining TH signal accounted for one-third of the TH signal of control mice. This smaller signal strongly resembled the VTA/SNc innervation to the dCA1 seen using the synaptophysin anterograde tracing approach, indicating that it represents the midbrain dopaminergic input.To differentiate the VTA/SNc and LC sources further, Tsetsenis et al.  generateh current amplitude, input resistance, resting membrane potential) typical of dopaminergic neurons . MEK in turn acts to inactivate AI channels  in specific timing protocols  task  ratio of hippocampal slices extractedIn contrast, inhibitory avoidance (IA) footshock training in a distinct context produced plasticity in a different circuit of the hippocampus. In this task, mice are in a well-lighted space, and a door opens to a dark, unlit space. The mice quickly move to the dark space where they are given a footshock. Thus, in subsequent trials, the mice delay entering the dark space when the door opens. IA training produced an increase in the A/N ratio in the synapses arising from the Schaffer collateral/CA1 pathway, but synapses in the perforant pathway remain unchanged  amplitude, and the hippocampal synaptic potentiation was contingent upon intact DAergic neurotransmission. Specifically, the administration of D1 receptor antagonists just prior to and during training blocked the acquisition of long-term memory and the changes in the fEPSP.in vivo from freely moving animals, is the fEPSP. The fEPSP measures the postsynaptic responses of a neuronal population in the vicinity of the recording electrode , another hippocampus-dependent task of associative learning  pathway and directly from the entorhinal cortex via the temporoammonic (TA) pathway. DA may act to rebalance the relative weights of SC and TA inputs by modulating the intrinsic and synaptic properties of hippocampal GABAergic interneurons, in a similar manner to the effects recently shown for acetylcholine (Palacios-Filardo et al., The experimental evidence reviewed here strongly supports an important modulatory role for DA in the regulation of long-term plasticity in the hippocampus with direct effects on learning and memory. This neuromodulatory action is largely mediated by activation of D1-type receptors in the dorsal hippocampus, which facilitates LTP and promotes spatial and contextual information encoding and storage (Hansen and Manahan-Vaughan, via activation of LC-VTA inputs (Simon et al., Another level of complexity in deciphering the function of hippocampal DA in regulating cognitive processes is added when one considers the origin of the dopaminergic signal. Recent evidence from studies using optogenetic methods to enhance DA release in the dorsal hippocampus showed that both the VTA/SNc and the LC can release DA in the dCA1 to facilitate specialized aspects of learning . How theTT and JB wrote the initial draft of the manuscript. JD edited and wrote the final manuscript and contributed with financial support. All authors contributed to the article and approved the submitted version.


The inclusion of women in vaccine trials has been marginalized over the years, which resulted in unwanted high dosage administration of vaccines in women.The intricacies in various signaling routes involved in the menstrual cycle can be impacted by internal as well as external stimuli, and the role of stress, be it physical, psychological, or social, in disturbing the process could be debilitating for a woman. The global endeavor of vaccination rose to protect individuals from the severity of COVID-19, but a conjunction of a short-lived menace of menstrual disturbance in the female population came out as an unsettling side effect. An understanding of the immunological panorama in the female reproductive tract (FRT) becomes important to fathom this issue. The close-knit microenvironment in the FRT shows active microbiota in the lower FRT, but the latest findings are ascertaining the presence of low-biomass microbiota in the upper FRT as well. Concerted signaling, wherein inflammation becomes an underlying phenomenon, results when a stressor elicits molecules of the inflammatory cascade. Learning lessons from the gut microbiota, we need to address the exploration of how FRT microbiota would impose inflammation by manipulating the immune response to vaccines. Since there is a prominent sex bias in the immune response to infectious diseases in women and men, the role of sex hormones and cortisol becomes important. The treatment regimen may be considered differently in women who also consider their ovarian cycle phases. Women exert robust immune response to antigenic encounters  The complex function of regular menstruation is under the systemic endocrine control of secretions from the hypothalamus, pituitary gland, ovaries, and uterus endometrium. Methodical ovulation and hence menstruation gauge the overall wellbeing of a female body, which has been indexed as the “fifth vital sign.” The intricate chemistry of various signaling events occurring during menstruation is highly impacted by the internal as well as external stimuli, which often shows as short-lived changes in the regular pattern of menstrual periodicity and/or characteristics in every woman (like intensity and duration of bleeding as well as the accompanying pain).The female reproductive tract (FRT) is a highly malleable signaling cascade; it can withstand stressors through the short-term manifestation of changes in the menstrual pattern. Inflammation may lead to suppression of ovarian function. The global endeavor of vaccination rose to protect individuals from the severity of COVID-19, but the conjunction of a short-lived menace of menstrual disturbance in the female population came out as an unsettling side effect.Here in this review, we have analyzed the possible mechanisms that might be playing roles in the menstrual disturbances after COVID-19 vaccination.The unprecedented development of the COVID-19 vaccine marks itself as a savior during the days of the COVID-19 pandemic . The mosAlthough the change in the menstrual pattern after vaccination is not universal, its effect is quite significant. According to the UK Medicine and Healthcare products Regulatory Agency (MHRA), 39,591 suspected cases of menstrual disturbance were reported, wherein the prominent vaccine candidates were AstraZeneca, Pfizer, and Moderna .In another study on the Norwegian young adult cohort, significant disturbance in the menstrual cycle was reported, which included a heavier bleeding pattern, an increase in the duration of menstruation, and a shortening of interval between two cycles .Although the study by Edelman et al. identified small changes in cycle length, which might not be of concern with respect to the clinical range of 8 days or more (change in cycle length), the data from such studies are still valuable for individual planning or avoiding pregnancy. The same study recorded 358 women who were vaccinated with both doses in the same cycle, and interestingly this group had 10.6% of women who experienced a change in the length of their menstrual cycle for more than 8 days. However, the cycle length in all the groups under study returned to normal after two cycles .The administration of prophylactic vaccines for human papillomavirus (HPV) is currently under use for preventing cervical cancer . HoweverThe immunological panorama of the uterus keeps changing with the menstrual cycle. The mucosa of the FRT displays a plethora of immune activity. The uterus and fallopian tubes, which are in the upper reproductive tract, sporadically become exposed to a burst of various antigens like sperm or fetal-placental organization, whereas the lower reproductive tract comprising the vagina and cervix harbors a niche of the microbiome that altogether represents a different antigenic stimulus. The multiple layers of the squamous epithelial lining of the lower reproductive tract lack tight junctions, whereas the upper single-layered epithelium has tightly bound columnar cells. This is important, as the transition zone between the two epithelia acts as a major effector and site of induction for cell-mediated immunity {reviewed in }. ContraThe pattern recognition receptors (PRRs) rise as the first line of defense in the vaginal tract. The toll-like receptors (TLRs) expressed on uterine epithelia elicit inflammatory response {reviewed in }. There Neutrophils, macrophages, and dendritic cells (DCs) are highly distributed in the upper FRT. Activation of memory T cells by macrophages and DCs acts as a bridge between innate and adaptive responses. Before ovulation, innate lymphoid cells (ILCs) are low in number, but they increase swiftly after ovulation. The immune reaction in the lower FRT keeps shifting during the menstrual cycle, increasing susceptibility toward infection {reviewed in }.+ T cells and immunoglobulins (Ig) but also with more incidences of autoimmune disorders {reviewed in , a sentinel of the acute innate response, has been associated with fluctuations in ovarian hormones during changes in the phases of the menstrual cycle . The intAlthough the immune response in women to infectious diseases like viral infection is robustly juxtaposed with that in men, the incidences of autoimmune disorders are higher in women {reviewed in }. SumminThe clinical implication of sex bias toward infectious studies is much needed where a detailed consideration on the account of drug pharmacokinetics in men and women should be addressed. Women mounted frequent and severe adverse reactions to HIV antiretroviral therapy {reviewed in }. The efThe long-thought paradigm about a sterile uterus has been well challenged by reports of bacterial colonization in the uterine environment , 25. TheAn astonishing concept of gender bias, termed “microgenderome,” was suggested wherein the commensal microbiota exercised gender bias by regulating sex hormones . The conThe impact of bacterial colonization definitely affects the immune cells of the uterine mucosa. For successful commensalism, the uterine mucosa needs to protect itself against any potential tissue invasion, which forms the basis of suggested immunological barriers seen across the homeostasis in the intestinal microbiome. As described by Hooper and Macpherson, three immunological barriers act to establish the equilibrium: the exposure of the microbial community to immune cells is limited, mediators of immune cascade keep a check on the direct contact between microbe and epithelium, and highly coordinated detection and destruction of breaching microbes . The endThe uterine leukocyte contains 10%–20% of macrophages (MΦ) and DCs, which constitute the antigen-presenting cells (APCs). The late secretory phase of the menstrual cycle shows mature APCs and MΦ along with NK cells as major producers of cytokines in the endometrium. T cells are residents of the deep endometrial layer {reviewed in }. The stThe DCs are important when it comes to introducing antigens of vaccine to T cells. The plethora of immune reactions controlled by PRRs has been shown to be modulated by microbiota, which directly affects DCs. This was shown well in the case of the intranasal inactive cholera toxin vaccine. The TLR-mediated antigen sensing by DCs in the lung lining led to the activation of gut-homing receptors, whereas the production of IgA in a TLR-dependent way was diminished in cases where microbiota was depleted due to broad-spectrum antibiotics {reviewed in }. The siThe microbiota can strikingly impose itself as a biological adjuvant on the response of vaccine {reviewed in }. The coMicrobiota might be a key factor in modulating uterus immunology  by the hypothalamus, which further stimulates the pituitary to release FSH and luteinizing hormone (LH). The ovaries produce sex-steroid hormones, estrogen, and progesterone, which control the development of follicles, maturation, and release of oocytes under the control of FSH and LH.The hypothalamus-pituitary-adrenal (HPA) axis controls the production as well as secretion of cortisol hormones in the adrenal cortex through corticotropin-releasing hormone (CRH). Cortisol, being a steroid hormone, is essentially a glucocorticoid that affects reproductive organs as well as response to stress, inflammation, and immune functions {reviewed in }. Under via cell-mediated and humoral arms. Markle et al. provided remarkable insights into the immune response due to the effect of sex on the transcriptome and microbiome. The environmental factors can affect the way sex hormones act during an immune response (A plethora of studies now testify that men and women are affected differently by diseases {reviewed in }. Women response .The inclusion of women in vaccine trials has been marginalized, which resulted in unwanted high dosage administration of vaccines in women. Women in the age range of 18–64 years were seen to generate vigorously antibodies against the influenza vaccine; moreover, their reaction to a half dose of the vaccine was equivalent to the reaction of men who received a full dose {reviewed in }. Despit+ and CD8+ T-cell response to SARS-CoV-2 (Vaccines with mRNA and adenovirus-vector bases have been shown to elicit higher levels of CD4RS-CoV-2 . StudiesEdelman et al. have proposed that the robust immune reaction stimulated by an mRNA vaccine could be a potential stressor affecting the hypothalamus-pituitary-ovarian axis . They haStress is any physical or psychological tension that threatens the homeostasis of an organism. The situation of the COVID-19 pandemic exposed individuals to psychological stress, and the decision to undergo vaccination against the SARS-CoV-2 was a part of it. The news pouring in about menstrual irregularities after vaccination stemmed from the willingness of women to be vaccinated , 42. TheThe stimulation of the HPA axis under stress results in cortisol elevation, which exerts a global effect on body functioning. Hitherto, studies on the effect of stress resulting in dysbiosis majorly includes majorly the gut  and vagiAs per our discussion elsewhere, the oral microbiome showed the effects of microbial endocrinology. This phenomenon is applied in FRT microbiome studies and might help in ascertaining the outcomes of infections as well as vaccination. Therefore, a comprehensive elucidation of the effect of stress on uterine dysbiosis is warranted.It is now undebatable that COVID-19 vaccination has protected against the severity of the disease. The world population grappled with the problems caused by the infection of SARS-CoV-2, and being vaccinated boosted our confidence to face this situation. However, the issue of menstrual irregularities in the female population after vaccination is something that needs attention. The issue of postvaccination menstrual disturbance is medically very important with respect to female wellbeing because an unexpected event causes anxiety. We must design studies acknowledging the vulnerable groups like those with autoimmune disorders or preexisting gynecological issues so that they can be counseled appropriately before vaccination. An editorial by Victoria Male has highlighted one misinformation being disseminated to the public that the COVID-19 vaccine leads to infertility in women . So the Since the advent of vaccines, not only humans but also animals and plants have benefitted. The female population deserves to be considered with respect to their biological constitution in vaccine trials. The literature on issues like this is scarce. Hence it is high time to encourage female-specific vaccine research to address subjects like menstrual disturbance, which, even though short-lived, impacts women physically, emotionally, and socially.RM contributed to the conception and design of the study. SR, AA, DD, and AS contributed to the revision and read and approved the submitted version of the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.Some citations are from non-peer-reviewed websites. Therefore, expert discretion is advised.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The purpose of this systematic review was to evaluate the clinical and laboratory outcomes of angled screw channel (ASC) restorations and to summarize the influencing factors. An electronic search of the English language literature was performed in four databases and enriched by manual searches. Retrieved studies were screened against the predefined exclusion and inclusion criteria. Eight clinical and seven laboratory studies were eligible for the analysis. The risk of bias for included observational studies was performed using the Newcastle–Ottawa quality assessment scale. Laboratory studies quality assessment method was adapted from previous published systematic reviews. Two clinical studies focused on technical outcomes and the rest reported the biological outcomes of the ASC restorations. Out of the seven laboratory studies, two studies investigated the fracture resistance of ASC restorations, four studies evaluated the reverse torque value of the nonaxially tightened screws, and one study evaluated both variables. The present review revealed that while the performance of ASC restorations is promising in short-term clinical studies, the evidence of their long-term reliability is still lacking. The laboratory studies indicated comparable fracture resistance results of the ASC restorations with the straight screw channel restorations. In addition, factors, such as initial torque value, configuration of the screw driver, screw design, abutment system, and the angulation of screw channel, were shown to influence the screw resistance to loosening. The implant-supported prosthesis is a successful strategy to restore dental esthetics and function.Almost two decades ago, angled screw channel (ASC) abutment design  was introduced to allow restoring angulated implants with simple direct to fixture screw-retained restoration. The ASC design uses a screw with a hexalobular head shape that can be engaged with a hexagonal faceted sphere screwdriver at various angles between 0 and 28 degrees with 360-degree freedom of rotation.This systematic review adapted the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The aim was to answer the following focused question “what are the outcomes of implants restored with angled screw channel prostheses?”The main search strategy was developed for PubMed  and supThe initial electronic search yielded 358 publications. After elimination of duplicates, 326 remained for title and abstract review. Twenty-seven articles were selected for full-text analysis, 13 of which were laboratory and clinical studies that fulfilled the inclusion criteria. Fourteen studies were excluded as listed inDrew et alIn the same study, Goldberg et alHu et alSwamidass et alOverall outcomes from the seven clinical studies showed a high survival rate for both the ASC restorations (88–100%) and the dental implants (98–100%) with low mean marginal bone loss . However, the majority of the studies were conducted for a short duration of time (1 year). Ceramic fracture was the most frequent complication that was reported in three studies (seven events),Two studies included data for ASC and SSC restorations.This systematic review critically appraised the existing evidence from the laboratory and the clinical studies on the implant-supported ASC restorations. Concerning laboratory studies, fracture strength and screw resistance to loosening were investigated. According to fracture strength studies, the ASC restorations appear to fail at less cycles of loads and lower forces than SSC. However, since they sustained the expected physiological forces, the ASC restorations were considered mechanically comparable with SSC counterparts.When resistance to screw loosening is considered, studies showed that the RTV was influenced by initial torque value,Intimate engagement of the screwdriver and screw head showed to play a role in the amount of the delivered torque. This is further influenced by the screwdriver's sphere and facet design, as well as, the surface treatment of the screw head.The use of nongenuine component can influence the RTV and may jeopardize the joint stability of the implant-abutment complex.The majority of the included clinical studies reported no major complications after 1 year of treatment of posterior regions with conical connection Nobel Biocare implants and ASC restorations.The data on MBL around the ASC restorations revealed favorable outcomes. Previous systematic reviews have indicated that changes in the crestal bone level is not significantly affected by angulated implant placement as compared with axial placement.While ASC restorations show promising short-term results, some clinical questions are yet to be answered. For example, there is a need to determine their long-term clinical performance, cost-effectiveness, and the management of their complications. Thus, the availability of ASC should not be a justification for injudicious angular implant placement.The present systematic review is limited with the fact that few clinical studies provided clear comparison between ASC and SSC. In addition, the fair quality of the majority of clinical studies and high-to-medium risk of bias of the laboratory mandate the need for stronger future evidences. Another limitation is that the clinical data were incomplete regarding the amount of angle correction. Moreover, most of the clinical studies had only 1-year duration of observation which does not reflect the long-term performance of ASC. Thus, the current evidence for use of ASC is limited and a more robust clinical guidance on the application of ASC abutments is needed.Within the limitation of this systematic review, the following inferences can be drawn:According to laboratory studies, the fracture resistance of SSC and ASC restorations were comparable. The incidence of screw loosening might be lower in ASC systems with higher insertion torque and genuine components.According to clinical studies, although the ASC restorations demonstrated favorable performance in anterior and posterior regions of the mouth in short-term, evidence is insufficient to determine their long-term survival.


We present a case of a surgically treated latissimus dorsi (LD) and teres major (TM) tear with a one-year outcome. The postoperative course was complicated by wound dehiscence requiring operative intervention and neuropraxia of the posterior cutaneous nerve of the arm. The report highlights previously unreported surgical risks associated with repair of LD/TM tendons. Tears of the latissimus dorsi (LD) and teres major (TM) are relatively uncommon and are typically observed in professional and high-level recreational athletes. Insertion of the LD and TM away from the humerus' axis of rotation subjects these tendon units to extreme forces in activities like overhead sports and cable watersports . While LThere is no consensus regarding ideal treatment of LD/TM tears as both surgical and nonsurgical interventions have been reported with comparable outcomes , 3. As sThe index patient is a 31-year-old right-handed dominant male who presented after a wakeboarding accident in which he heard an audible pop accompanied by sharp left shoulder pain after a sudden pull by a tow cable. Physical examination was remarkable for extensive ecchymosis around the posterior aspect of the arm and left hemithorax, as well as swelling in the posterior axillary region . MagnetiPrimary repair of the LD and TM tendons was performed in a sloppy lateral position via a single axillary-based incision (Video 1). The posterior cutaneous branch (PCN) of the radial nerve was identified and protected during subcutaneous dissection. Deep dissection demonstrated a seroma covering the stumps of the torn LD and TM tendons, which were avulsed off their insertion from the bicipital groove.Both tendons were mobilized and able to reach their insertional footprint for a direct primary repair . Two higPostoperatively, the arm was placed in a sling for six weeks. Active adduction and internal rotation, passive overhead abduction, and external rotation were not permitted during this initial phase of immobilization. Active ROM was started at six weeks with the introduction of LD and TM strengthening exercises at three months.The patient reported serous drainage from the incision and was found to have wound dehiscence in the central part of the incision (1 cm) three weeks after surgery. He underwent irrigation and debridement in the operating room with primary wound closure, and the incision healed uneventfully thereafter. The patient also reported decreased sensation in the distribution of the PCN of the arm. The sensation progressively improved throughout the year after surgery. The primary repair and PCN of the arm were both intact upon observation during the debridement surgery.At one-year follow-up, the patient reported no pain and was able to return to preinjury sporting activity without limitations. He had normal contour of the left posterior axillary fold and full shoulder ROM . He rateSurgical repair of LD and TM offers improvement in strength in adduction and extension, as well as cosmetic improvement in the posterior axillary fold contour. Despite these advantages, the close proximity of the surgical site to neurovascular structures poses an inherent risk for injury . In thisThe PCN of the arm is encountered in an axillary-based approach for LD repair and is at risk for injury. However, this complication has not been previously reported with LD/TM tendon repairs. As the presentation for PCN of the arm neuropraxia can vary and potentially be underreported, awareness of this complication is pertinent to patients undergoing repair and those treating them. Previously reported neuropathies in studies involving LD tendon transfers include those of the axillary nerve, ulnar nerve, and brachial plexus injury . In our There continues to be debate regarding ideal treatment of LD/TM tendon tears. Surgical treatment is an acceptable treatment option for combined LD and TM tendon tears, but patients must be counseled for potential risks and complications. Although there is paucity of literature on surgical outcomes, wound complications and neurological injuries are important risks in addition to retear or failure of repair.


Chronic kidney disease (CKD) remains to be one of the highest public health burdens worldwide with high-prevalence among the general population. The heterogeneity of the underlying disorders and stages of progression, as well as the lack of clear symptoms makes the whole healthcare process challenging not only for treatment but also for proactive and preventive care of the patients .Application of Proteomics in Kidney Diseases” is to emphasize the importance of the identification and investigation of new and more reliable biomarkers that likely will improve early and accurate diagnosis of CKD, especially in context of improved patient stratification and prediction of disease outcome or treatment response. We are grateful to all of the authors for their valuable contribution to the present Research Topic and for the willingness to share some insights of their expertise with the research community to open new avenues for further improvement of CKD management.Currently available diagnostic markers are in many cases only indicative for late CKD stages and are not significantly superior in their accuracy to the estimation of the glomerular filtration rate (GFR), urine albumin to creatinine ratio (ACR) or immunohistochemically assessment of kidney biopsies. Although identification and characterization of various biomarkers  in different body fluids using high-resolution techniques for biomarker-guided therapies have been a major focus for the clinical research in the last years, globally up to 16% of the people with a high-risk of CKD development are potentially unprotected . TherefoLi et al. in their well-structured review have highlighted the role of Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, in providing beneficial cytoprotective properties in cell metabolism. The authors outlined the involvement of HO-1 in regulation of oxidative stress and pathogenesis in various renal diseases. They provide a comprehensive overview of multiple studies elucidating the enzyme's function in metabolic processes for cell proliferation and cell maturation. Great emphasis was also laid to the description of therapeutic strategies where HO-1-overexpressing macrophages are used for treatment of kidney diseases.Until to date, progress have been made for the application of proteomics in CKD. Development of biomarkers and identification of appropriate therapeutic targets are important aspects where scientists/clinical experts have put their focus on. In fact, early detection and prognosis of CKD including differential diagnosis and monitoring of drug treatment are areas with the greatest clinical need. Along these lines, Zhou et al. have studied the effects of Transient receptor potential (TRP) C5 channel inhibition in puromycin aminonucleoside (PAN)-treated rats, in human iPSC-derived podocytes, and in kidney organoids. The authors were able to confirm that TRPC5 inhibition throughout AC1903 blockage in PAN-induced nephrosis rats protects podocyte cytoskeletal proteins from degradation and decrease levels of proteinuria. In a similar manner, inhibition of TRPC5 channels in 2D and 3D iPSC and organoid cell cultures altered the effect PAN-induced injury in human podocytes, providing evidence for targeting TRPC5 channels in the development of new potential CKD therapeutic strategies for patient care.Current clinical markers like deceased GFR function and/or presence of proteinuria are commonly considered as a gold standard for CKD diagnosis and its progression . To imprShen et al. Evaluated levels of urinary β2-microglobulin (β2-MG) and Retinol-binding protein (RBP) have been assessed using restricted cubic splines and Cox proportional hazards models. As a result, the authors demonstrated that baseline levels of β2-MG and RBP were correlated with proteinuria, eGFR and histopathological Oxford classification IF/TA T scores. It was found by the authors that higher levels of β2-MG and RBP are indicative for worse outcome and disease progression in IgA nephropathy, highlighting the importance and prognostic utility of such non-invasive biomarkers in a clinical setting. Using a similar approach, Zhang et al. examined in a case-control study 6 potential plasma biomarkers that might be of clinical value in the prediction and patient stratification of acute kidney injury (AKI) progression after cardiac surgery. Out of the 6 investigated biomarker candidates, three demonstrated superior predictive capabilities and were further validated in an independent patient cohort. A marker panel consisting of these 3 markers, namely growth differentiation factor 15 (GDF15), soluble suppression of tumorigenicity 2 , and soluble urokinase plasminogen activator receptor (uPAR) outperformed current clinical parameter models in their predictive performance.The potential application of two clinically important biomarkers for disease progression in IgA nephropathy has been investigated in a retrospective study with 2,153 patients by Xu et al. reported a rare case of ARPKD where two siblings harbored biallelic variants in PKHD1 (c.7205G>A and c.7973T>A) were identified. In their clinical case study, pathological analysis showed several well-known transformations of the renal tubules and collecting ducts. In addition, urinary exosome analysis confirmed decreased expression of proteins from the mitochondrial oxidative phosphorylation system (OXPHOS) which is involved in glycolysis, but also increased expression of lysosomal N-sulfoglucosamine sulfohydrolase (SGSH). Altogether, these findings provide new insights into the pathophysiology of the polycystic kidney caused by PKHD1 deficiency. Another extremely rare but clinical important disease is urological malakoplakia. It is characterized by the absence of any symptoms and induced by pathophysiological alterations in the phagocytotic system. Malakoplakia affects any part of the human body but most frequently occurs in the urinary system. In a clinical case study, Wang and Ren provided some insights into disease etiology with specific emphasis on the complexity of its diagnosis and distinction from infections, tuberculosis, as well as benign and malignant tumors of the urinary tract. The diagnosis and pathogenesis of malakoplakia is closely related to chronic infection and an impaired immune system. Although the authors suggested several clinical parameters for consideration, it was outlined in their report that the disease is mainly diagnosed by pathological examination. However, it should be emphasized that patients with such clinical manifestation are encouraged to visit their physicians more frequently in order to better elaborate the disease background.The underlying cause of a kidney disease is from patient to patient highly variable. Some of the patients could have rare genetic mutations mediating slow growth of the kidneys, ultimately leading to late phase of disease progression often without possibility of any intervention. Autosomal recessive polycystic kidney disease (ARPKD) is one of them which is a heterogeneous genetic disease of the kidneys mainly affecting infants and children . It is cOver the past decades, proteomic methodologies as well as novel laboratory technology have been proven to play a key role in providing important molecular information about disease processes. Knowing the fact that proteome profiles can reveal altered molecular pathways in CKD on top of the clinical/histopathological assessment, it is evident that their implementation in daily clinical routine is of unmet need. Certainty, clinical studies dealing with application of new drug targets supported by the biomarkers to predict and monitor CKD disease progression is expected to increase in the next years.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.MP, PM, and JM were employed by Mosaiques Diagnostics and Therapeutics AG.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Faculty development programs (FDPs) are an effective, evidence-based method of promoting the knowledge, skills and self-efficacy of faculty. However, the implementation and sustainability of curricula are rarely reported. Furthermore, the challenges to sustaining programmatic implementation of interprofessional FDP curricula in academic and clinical settings over time have yet to be extensively evaluated. Using dynamic sustainability as a framework, we aimed to assess the evolving barriers and facilitators that influence the implementation and sustainability of the geriatrics curriculum Capstone projects designed by faculty scholars in our FDP. We planned to report on projects that were and weren't successful. A survey, sent to 115 faculty scholars from eight different cohorts who completed our 10-month FDP, recruited faculty participants and set the stage for qualitative data collection to help us better understand the sustained impact of the program. Thematic analysis of virtual interviews with 17 Scholars revealed several key factors facilitating and hindering the implementation and dynamic sustainability of curricular projects. Three major themes and sub-themes were identified as follows: Project Implementation ; Pedagogical Development (Enhancement of Skills and Culture Change); and Sustainability Impact . Supporting these factors through skills development may favorably impact project sustainability and thus the aspects of workforce development that catalyze practice change. Implementation of geriatrics-focused FDPs provides an evidence-based approach to sustainability. Further study of the ongoing barriers and facilitators to sustainability is encouraged.


The leakage of underground natural gas has a negative impact on the environment and safety. Trace amounts of gas leak concentration cannot reach the threshold for direct detection. The low concentration of natural gas can cause changes in surface vegetation, so remote sensing can be used to detect micro-leakage indirectly. This study used infrared thermal imaging combined with deep learning methods to detect natural gas micro-leakage areas and revealed the different canopy temperature characteristics of four vegetation varieties  under natural gas stress from 2017 to 2019. The correlation analysis between natural gas concentration and canopy temperature showed that the canopy temperature of vegetation increased under gas stress. A GoogLeNet model with Bilinear pooling (GLNB) was proposed for the classification of different vegetation varieties under natural gas micro-leakage stress. Further, transfer learning is used to improve the model training process and classification efficiency. The proposed methods achieved 95.33% average accuracy, 95.02% average recall and 95.52% average specificity of stress classification for four vegetation varieties. Finally, based on Grad-Cam and the quasi-circular spatial distribution rules of gas stressed areas, the range of natural gas micro-leakage stress areas under different vegetation and stress durations was detected. Taken together, this study demonstrated the potential of using thermal infrared imaging and deep learning in identifying gas-stressed vegetation, which was of great value for detecting the location of natural gas micro-leakage. Natural gas, as a clean energy source, has continued to attain sustained growth in consumption in recent years ,2. With Traditional natural gas leakage detection mainly includes manual inspection , sound mThe study of canopy temperature is mostly based on the average data measured from areas or points, which may be more useful than individual leaf temperatures in detecting vegetation stress . HoweverThe aim of this study was to detect natural gas micro-leakage stress areas in four vegetation varieties using infrared thermal images with deep learning methods. The objectives were as follows: (a) to explore the correlation between gas concentration and vegetation canopy temperature under natural gas micro-leakage stress; (b) to classify the natural gas stress of four species of vegetation based on the CNN; (c) to improve the efficiency of the classification model based on transfer learning; (d) to detect natural gas micro-leakage areas and time series analysis.The impact of natural gas micro-leakage on vegetation was studied by field simulation experiments to indirectly detect natural gas micro-leakage areas. The experiment field was located in Daxing District, Beijing, with coordinates of 39°39′2.56″ N, 116°34′33.10″ E. As shown in This experiment lasted from 2017 to 2019. Each plot received the same standard agronomic practices such as watering, fertilization, weeding, pest control and uniform seedling during the experiment, which can ensure that the vegetation was unacted on the other controllable factors.In this experiment, ten gas concentration sampling points were evenly distributed in the experimental plot to determine the concentration of natural gas in the soil. Three hollow PVC pipes were inserted into each sampling point, with a depth of 60 cm underground. Since the main component of natural gas is methane, a GXH-3050E gas analyzer  was used to collect the methane concentration of each point every three days during the whole experimental period a. The avFluke ti55ft thermal imager  was used for data acquisition b. The thThe infrared thermal images taken in the field were processed in smartview4.3 software . The data collected from field experiments needed to be removed for singular values before comparative analysis due to the influence of metal marker points. In addition, deep learning approaches require a large number of training samples to learn the weights and parameters in the training phase ,48. Due Compared with the traditional model, the deep learning approaches provide better results for the recognition and classification of agricultural images . In thisTransfer learning pre-trains the model and retains the parameters of the model. Then, a small amount of target data is used to retrain the fully connected layer. This approach can optimize the learning efficiency of the model and improves the model performance ,52. Howec, the weight (Gradient-weighted Class Activation Mapping (Grad-CAM) assigns the gradient information of the last convolution layer to each neuron and generates a location map to highlight the important region in the image, which is the basis of output prediction . The lasc, the classification localization map (Equation (1) can be intuitively understood as: take the input (Equation (2) can be intuitively understood as: the input of different neurons in the last convolutional layer are multiplied by their respective neuron weights. Then the corresponding values of all neurons are summed. The In this paper, the confusion matrix was used to evaluate the classification performance of the CNN model. Accuracy represents the proportion of all correctly matched samples to all samples. However, when the number among different samples is unbalanced, there is a great error in using the accuracy as the index. Multiple evaluation indexes being used to comprehensively evaluate the model can more truly reflect the effect of the model. Therefore, the accuracy, recall and specificity were used to evaluate the performance of the model in this study. The following is the formula:Cynodon dactylon L.), soybean (Glycine max Merr.), corn (Zea mays L.) and wheat (Triticum aestivum L.), respectively. Soybean, wheat and corn are one of the main crops in China. Grass is a good plant for Embankment Consolidation and soil conservation, which is often used to pave lawn for urban greening. The four types of vegetation have different characteristics and are widely planted in China.The infrared thermal image could not cover the whole plot because of the small field angle of the infrared thermal imager. But it could cover the main stress area in the experimental plot. Infrared thermal images of the four vegetation in the experimental plot and the control plot are shown in As shown in According to the statistical characteristic values of temperature distribution , the meaThe infrared thermal image was matched and superimposed with the gas concentration distribution map as shown in Infrared thermal images of four plants were input into the GLNB model for 200 epochs training. It was found by many attempts that a large learning rate could cause the loss curve to oscillate and the model failed to fit, while a small learning rate could cause slow convergence of the loss curve and overfitting of the model. Therefore, 0.0001 was applied to the proposed model as the appropriate learning rate. Adam made the model converge faster by comparing the performance between Stochastic Gradient Descent (SGD) and Adam, so Adam was applied to the proposed model. In addition, four classical CNN models  than other kinds of plants . Similar results were obtained in the other four classical models. Grass had a higher stress recognition rate rather than soybean, corn and wheat, which showed more sensitive to the nature gas. There may be the following reasons. The different canopy structure makes the irregular stress shape of corn, soybean and wheat, which makes large identification errors. Corns are taller with sparse planting spacing, which is easy to produce shadow and causes recognition error. Wheats have tufted and thin stalks, which is easy to cause uneven canopy coverage. Soybeans have strong rhizomes with large coverage of single plant. Meanwhile, the soybean rhizobia are easy to affect the stress symptoms of natural gas. Ferchichi  found thThe GLNB-based transfer learning model (GLNB-TL) was developed to use public datasets as the training set to pre-train the model and obtained the corresponding model structure and weights. The iterative curves of the GLNB and GLNB-TL during training are shown in The test results of GLNB and GLNB-TL are presented in Grad-CAM was used to generate the heatmap of class activation in this paper, which visualized the classification features of the input image. The last convolutional layer captured more specific features of the image, so Grad-CAM used the gradient information from the final convolutional layer of the model to generate heat map to understand the importance of each neuron for category recognition. Infrared thermal images of five periods were selected for each vegetation type. The stressed vegetation areas caused by natural gas micro-leakage were extracted by Grad-CAM and segmented based on the adaptive threshold method. Vegetation stress areas were consistent with natural gas micro-leakage areas, which had been demonstrated in Combined with the stress range of vegetation in different periods and their mean stress radii, the mean stress radius of grass was the largest. And the stress range showed a trend of steady expansion, which was consistent with the diffusion and accumulation pattern of natural gas leaked into the soil. The large density and the uniform canopy structure of grass and the more obvious stress symptoms make it easier to detect the stress caused by natural gas micro-leakage in the wild. Furthermore, the rhizomes of grass are highly spreading and well adapted to the field environment, which can reduce the time and cost of manual maintenance. Therefore, grass can be used as a good indicator to detect natural gas micro-leakage.In this study, infrared thermal images and natural gas concentration data from 2017, 2018, and 2019 were used to evaluate vegetation growth during the natural gas micro-leakage in the Daxing District of Beijing. It was found that the spatial distribution of natural gas in the soil was basically consistent with the temperature features of the stressed vegetation in the infrared thermal images. A deep learning method was proposed to identify stressed vegetation, thereby the area of natural gas micro-leakage can be detected indirectly. The proposed GLNB model for stress detection on grass, corn, soybean and wheat presented the better performance comparing with four classical CNN models. Furthermore, transfer learning was used to pretrain the GLNB model and the result showed that this method improved classification efficiency and detection accuracy. Finally, the range of stressed vegetation under natural gas micro-leakage was located based on GLNB and Grad-CAM. The time series analysis results showed that the generality and high efficiency of the proposed GLNB model made it applicable to multiple periods and various field plants, which overcame the challenge in terms of irregularity in the outdoor environment. However, there is still a scope for improvement. The response of stressed vegetation in canopy temperature is slow, so hyperspectral remote sensing technology can be added to study the spectral reflectance of vegetation for the early detection of natural gas micro-leakage areas. In addition, large-scale detection of natural gas micro-leakage can be realized by UAV technology as a future scope.


Many types of tumors can arise in the esophagogastric junction (EGJ). Squamous cell carcinoma (SCC) arising from the esophageal epithelia, adenocarcinoma arising from the gastric mucosa, or Barrett’s esophageal mucosa are frequently observed in the EGJ. However, adenosquamous carcinoma (ASC) has been rarely observed in this area. We herein report a rare case of ASC of the EGJ.An 81-year-old man visited our hospital complaining of dysphagia. Esophagogastroduodenoscopy detected an elevated tumor in the gastric cardia. Biopsy specimens taken from the tumor showed SCC. Computed tomography revealed a tumor located in the EGJ and node metastases surrounding the EGJ. The tumor was diagnosed as SCC, overhanging in the stomach, of the EGJ. The patient underwent a proximal gastrectomy with a lower esophagectomy and node dissection for the metastases surrounding the EGJ, and esophagogastrostomy in the lower mediastinum. Histopathologic examination showed the tumor consisted of SCC and adenocarcinoma. The adenocarcinoma consisted of nests scattered in the SCC. We observed adenocarcinoma component in 35% of the tumor and epithelial spread of SCC in the lower esophagus. Thus, we diagnosed the tumor as ASC of the EGJ. Eight metastatic nodes were dissected; both SCC and adenocarcinoma were observed in seven.In the present case, SCC may be originated from the squamous epithelia of the lower esophagus and grew into the stomach, and the adenocarcinoma may have differentiated from SCC through the infiltration. Tumors of the esophagogastric junction (EGJ) have many issues, including diagnosis and treatment . Squamou18F-fluorodeoxyglucose (FDG)-positron emission tomography, the standardized uptake value (SUV) max of FDG accumulation was 19.9 in the tumor  ASC was considered to be originated from the squamous epithelia; (2) ASC of the EGJ can present as a submucosal tumor-like mass in the EGJ, and (3) both SCC and adenocarcinoma were metastasized in regional nodes.No data of frequency of ASC in the EGJ is available. ASC is less frequently found in the esophagus. Previous studies reported it to be 0.37–1% of esophageal carcinoma in Western countries , and 0.6Various theories regarding the origin of ASC have been suggested in esophageal ASC. Pascal and Clearfield  reportedFive hypotheses have been proposed in gastric ASC: (1) squamous metaplastic transformation of adenocarcinoma –22; (2) It is interesting to note that the tumor was located in the stomach mainly with submucosal invasion, even though the origin of the tumor was considered to be the esophageal epithelium histopathologically. Kuwano et al.  proposedNode metastasis in ASC of the EGJ also remains poorly understood. Previous studies found that 33% of patients with esophageal ASC had node metastasis , 33. AmoWe report a rare case of ASC showing specific growing of the EGJ and discussed its growth pattern.


Sjogren’s Syndrome (SS) is heterogenous chronic autoimmune disease with symptoms ranging from organ-specific to variable non-specific systemic features. It is a rare disease in childhood and can be very difficult to diagnose, especially in seronegative patients, with the absence of any specific diagnostic investigation or criteria. We are presenting a seronegative juvenile Primary Sjogren’s syndrome (pSS) patient with all the challenges we had to confirm the diagnosis and a highlight on the role of MDT as the most sensitive tool.A 14-year-old female patient was first referred to our Paediatric and adolescent rheumatology department at the age of 10 with history of recurrent bilateral painful parotid swellings since the age of 3 with absence of ANA, RF, Anti-SSA-Ro and Anti-SSB-La antibodies repeatedly. From 2016 till 2019 she was under the care of ENT with recurrent complicated bilateral ear infections. Episodes tend to occur every 2-3 weeks and last between a few days to 2 weeks. Her events were associated with fever, fatigue, shivering, joint and leg pain, cervical lymphadenopathy, infrequent folliculitis, and headaches. No history to indicate mouth or eye dryness or significant repeated ulcers. Both of our patient’s mother and maternal grandmother have Behçet’s disease. Further blood investigation only showed mild hypergammaglobulinemia with mildly elevated ESR and CRP, normal LFT, U&Es, complements, muscle enzymes and thyroid function. HIV serology was negative and serum IgG4 subclass was normal. Many USSs confirmed parotitis. Parotid gland biopsy was not specific and indicated chronic parotitis with diffuse infiltration of mature lymphocytes, periductal lymphocytic inflammation and exocytosis of lymphocytes into the ductal epithelium. Focus score nearly reaching 50 cells. Plasma cell staining ruled out IgG4 related disease. Ophthalmic assessment ruled out eye involvement by the appearance of her eyes. The Oral Medicine Team confirmed the appearance of dry mucosa with minimal salivary flow from the parotid ducts, though it has not been subjectively reported to cause any problem before. Failed trial of colchicine, never been off-prednisolone for at least the last 2 years, tried Methotrexate which resulted in significant but not full improvement. Now she is on azathioprine and Hydroxychloquine, but still reporting flares. Escalation in treatment is required though there are some concerns about previous medication compliance, the actual severity of symptoms reported and the lack of current suitable accommodation.Diagnosing pSS is quite challenging especially in seronegative patients due to the possibility of other non-autoimmune diseases causing recurrent parotid gland swellings, especially Recurrent Juvenile Idiopathic Parotitis with very young age of onset. With the persistence of symptoms and lack of an underlying infection, our patient ended up having a parotid biopsy. This was generally not specific, with a focus score close to the 50 mononuclear cells required as evidence of exocrine inflammation. This further added to the challenge of confirming an underlying autoimmune disease. Nine years into the disease course, our patient was confirmed to have objective evidence of dry mucosa and decreased salivary flow from the parotid ducts. This shows how important it is to assess salivary and lacrimal gland dysfunction in a child with suspected pSS, despite the absence of typical xerophthalmia and xerostomia. Considering the non-typical features (sero-negativity and the non-specific histopathology findings), our patient clinical picture was discussed in an MDT meeting including ENT, Histopathology and Rheumatology and the diagnoses of pSS was confirmed. The chronicity of the disease, significant improvement of the flare frequency and severity while on immunosuppressants, the reoccurence of significant flares when the patient was off-treatment , and the objective evidence of poor salivary flow all supported the diagnosis of pSS later in the disease course. This case shows us how the typical adult features of pSS should not be strictly applied to the juvenile form of the disease. It also highlights the importance of having an MDT as the most sensitive available tool to confirm the diagnosis.Regarding lack of subjective full response, how do you think we can prove this objectively and what would be the most appropriate next step in treatment escalation?A high index of suspicion is crucial to reach the diagnosis and to avoid irreversible damage in children with SS.Quadrable sero-negativity should not be looked at as an absolute exclusion criterion of juvenile pSS.Exclusion of other more common and diverse causes of parotitis is crucial.The typical adult features of SS should not be strictly applied to the juvenile form of the disease.MDT approach is the most sensitive tool to diagnose SS.When there is no subjectively reported ophthalmic or oral dryness, we would advocate sending suspected children of pSS for formal assessment of it- we understand the age-related challenges.Considering its rarity, we need to improve the general awareness of the juvenile form of the disease among the population and the medical practitioners.


Reducing the Harm of medication: Recent Trends in Pharmacovigilance, following our first topic “Medication Harm: From Early Identification to Prevention”. Adverse drug reactions (ADRs) are considered to be among the leading causes of morbidity and mortality with very high economic costs. An estimated 5–25% of hospital admissions are due to ADRs, and 6–15% of hospitalized patients experience serious ADRs, causing significant prolongation of hospital stay. Moreover, fatal ADRs are estimated to occur in 0.31% of hospitalized patients [The Harm of Medication: From Early Identification to Prevention/Frontiers Research Topic]. Randomized controlled trials are the main premarketing methods used to detect and quantify ADRs but these have numerous limitations, such as the exclusion of patients at higher risk of ADRs , insufficient sample size for the detection of non-frequent ADRs, limited follow-up time for the detection of ADRs after long periods of exposure. In addition, the diagnosis of ADRs is complex and difficult in the Real World due to the non-specificity of ADR symptoms and signs, diagnostic tests are usually absent and a re-challenge is rarely ethically justified. At present, most countries participate in pharmacovigilance through spontaneous reporting systems of ADRs. However, spontaneous reporting systems have limitations such as under-reporting, of up to 90%, and reporting bias, of only ADRs easy to diagnose. Active pharmacovigilance programs may supplement such systems. In this Research Topic, we have had the opportunity to evaluate some of the latest strategies in pharmacovigilance programs to cover the much-needed timely and accurate identification of ADRs. Pharmacovigilance programs assessing ADRs occurring in routine clinical practice can contribute to a better knowledge of the risk profiles of a medication classes. A study using national health insurance data evaluated the association between antidepressant use dose/duration and cardiovascular disease (CVD) risk in patients without a history of CVD as a primary prevention measure Jang et al. The authors of this study found that even at low doses, the use of tricyclic antidepressants was associated with major adverse cardiovascular events. Further, the longer duration of tricyclic antidepressant use correlated significantly with a higher adjusted hazard ratio. In another national population-based retrospective cohort study the authors found that the use of “sleeping pills” was associated with an increased risk of chronic kidney disease. Liao et al.Two years ago, we launched this second Frontiers in Pharmacology Research Topic titled Shi et al. The authors found an inverse association between total epinephrine dosage during resuscitation and worse neurological outcome 3 months after the cardiac event. This study concluded that the early benefit of a medication does not ensure good results in the medium and long term among these patients. The pharmacovigilance system could investigate the functional status and quality of life of patients as indicators of the impact of ADRs. In another retrospective cohort study Kunming et al., the authors aimed to characterize vancomycin-associated acute kidney injury (AKI) in Chinese hospitals. The authors found a higher frequency of concomitant nephrotoxic medication use compared to their use in the USA and that the incidence of vancomycin-associated AKI was higher in patients with a combined use of nephrotoxic medications. The study recommended improving serum creatinine measurement for the AKI diagnosis and the standardization of vancomycin therapeutic drug monitoring. In a multicenter retrospective study exploring the association between mean serum vancomycin trough concentration (VTC) and mortality in Intensive Care Units Hou et al., the authors found that mean VTC was not associated with reduced ICU/hospital related mortality. These results indicate that further investigation is needed to address the issue of vancomycin dosing using mean VTC and support the recommendation of moving from trough levels to a 24-h area under the curve (AUC) to a minimum inhibitory concentration ratio. Another retrospective analysis was conducted on inpatients who received tigecycline treatment from January 2018 to January 2020 Shi et al. Based on the biochemical criteria of Drug-Induced Liver Injury (DILI) and the causality assessment by Roussel Uclaf Causality Assessment Method (RUCAM) using cases with a probable or highly probable causality grading. The author found that tigecycline was associated with liver injury, with a slightly higher incidence (5.7%) than the frequency of “frequent” (5%) defined by the Medical Dictionary for Regulatory Activities. In addition, tigecycline-associated DILI was related to a high maintenance dose, prolonged duration, and a number of concomitant medications with known hepatotoxicity.The use of hospital databases is essential for evaluating the safety of medicines for hospital use and for making decisions for the prevention of serious ADRs. In a retrospective cohort from an Intensive Care Unit (ICU), the effect on survival and neurological outcomes of full-dose epinephrine when used in cardiopulmonary resuscitation was investigated Frogerini et al., the association between PTGS1 and NOS3 variant alleles and the risk of developing upper gastrointestinal bleeding (UGIB) secondary to complicated peptic ulcer disease was assessed. The authors have shown an increased risk of UGIB in the presence of some genetic variants, regardless of the medication exposure. On the other hand, these genetic variants are said to modify the magnitude of the risk of UGIB in nonsteroidal anti-inflammatory drugs and low-dose aspirin users, since variants rs10306114 and rs5788 are related to a COX-1 with less capacity to produce prostaglandins and reduced platelet aggregation, respectively. Therefore the need for personalized therapy for the prevention of these serious ADRs is emphasized.It is well known that one of the major research challenges regarding drug safety is the identification of genetic variation of drug targets, drug-metabolizing enzymes, or drug transporters that can clarify the mechanisms of idiosyncratic ADRs. In the case-control study by Khouri et al. In a study based on suspected ADRs from the World Health Organization (WHO) global database (VigiBase) Allouchery et al. the authors conducted a disproportionality analysis of ibrutininb, a Bruton tyrosine kinase inhibitor for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, with respect all other anticancer medications used as the reference group in order to identify of potential safety signals. The authors combined the use of two complementary disproportionality measures  and found clinically relevant potential safety signals in patients exposed to ibrutinib, mainly ischemic heart diseases, pericarditis, uveitis, retinal disorders, and fractures. Immune checkpoint inhibitors (ICI) may be used to treat aggressive hematologic malignancies, either in refractory or relapsed lymphoma frequently before being treated by allogeneic hematopoietic stem cell transplantation  or in relapse after allo-HSCT. Nguyen et al. used the Bayesian estimate of disproportionality analysis of VigiBase to detect a signal of graft vs. host disease (GVHD), with subsequent mortality of 25.8%. This paper confirms previous results obtained from cohort studies on the association between GVHD and ICI. This manuscript is an example that the sum of evidence from different approaches in data analysis  would allow definitive conclusions and decision-making in pharmacovigilance. Conducting a systematic review and meta-analysis of randomized controlled trials, Man et al. addressed the putative increase risk of malignancies and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. The authors showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and an increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. Since the sparse number of events of malignancy and tuberculosis, these results need to be confirmed by further studies with a larger population and longer follow-ups.Automated screening tools developed from quantitative methods in the large databases of suspected ADR reports allow signal detection to trigger further investigations. Improving pharmacovigilance disproportionality analysis to reduce methodological heterogeneity and substantial variability of results by pre-registering the protocols and presenting a set of secondary and sensitivity analyses rather than a single result may prevent selective reporting of results Mardaniet al. On the other hand, high quality understandable, and accessible information helps patients to participate in decision-making about medicines prescribed for them by healthcare professionals. Despite a lot of information available in the media, patients considered patient information leaflets of medical products the most important source of information about medicines after medical prescription. Medina-Córdoba et al. evaluated patients’ cognitive, behavioral, and emotional factors and characteristics of Patient Information Leaflets that can promote appropriate drug use practices. Another study tried to identify factors associated with a lack of awareness of the impact of improperly disposed of medications among the general population in Bandung, Indonesia, and to assess the associations of awareness with medication disposal practices among this population. This study provides results that contribute to a better characterization of some aspects of patients’ medication self-management. Alfian et al.In this Research Topic, we have also evaluated the latest strategies to improve the safety of medication use. In this sense, an integrative systematic review of the practical considerations of Pro Re Nata medication management sought to summarize and integrate the practical considerations of healthcare professionals for the management of Pro Re Nata medications in different healthcare settings. Zdziarski et al. This general method could raise the hypothesis of drug-associated dysbiosis. When testing the method in one of the patients treated with high doses of inhaled corticosteroids, the authors have come across the unexpected finding that severe dysbiosis was followed by seronegative Sjögren’s syndrome.This topic also contains a case report with an objective to describe a simple, universal, and cost-effective method of microbiome analysis for clinical trials Vignot et al.Finally, a position paper from the ANSM  proposes some actions to be implemented to reduce the intentional unjustified use of medicines: 1) Early identification of situations in which inappropriate use can lead to a health risk comparing consumption in different countries. 2) Better collective engagement including educational programs and co-construction of action plans and improved communication with stakeholders Reducing the Harm of Medication - Recent Trends in Pharmacovigilance, Volume II/Frontiers Research Topic].We appreciate the good acceptance of this topic, and we will appreciate good reception among the authors to continue contributing effectively and share their interesting study findings in the second part of this topic (Volume II) [in vitro tests , in the diagnosis of ADRs. In this sense, the implementation of expert medical specialties in the diagnosis of ADRs  could give support and confidence to physicians in the generation of these new drug safety signals from primary and hospital care. On the other hand, electronic health records have proven to be more useful for evaluating problems already detected, allowing the implementation of prevention and early detection tools that minimize the risk of ADRs. Prospective cohort or retrospective observational database studies allow for longer follow-up periods of patients with a much broader range of characteristics, providing valuable means for the detection, quantification, and, where possible, reduction of ADRs, reducing health care costs in the process.Finally, we make some suggestions to encourage Pharmacovigilance activities going forward. The first is based on the fact that evidence suggests that individual case safety reports remain a very useful data source for detecting potential new safety issues. We suggest improving diagnostic tools, causality algorithms, and complementary drugs with other