The rapid development of diagnostic technologies in healthcare is leading to higher requirements for physicians to handle and integrate the heterogeneous, yet complementary data that are produced during routine practice. For instance, the personalized diagnosis and treatment planning for a single cancer patient relies on various images  and non-image data . However, such decision-making procedures can be subjective, qualitative, and have large inter-subject variabilities. With the recent advances in multimodal deep learning technologies, an increasingly large number of efforts have been devoted to a key question: how do we extract and aggregate multimodal information to ultimately provide more objective, quantitative computer-aided clinical decision making? This paper reviews the recent studies on dealing with such a question. Briefly, this review will include the (a) overview of current multimodal learning workflows, (b) summarization of multimodal fusion methods, (c) discussion of the performance, (d) applications in disease diagnosis and prognosis, and (e) challenges and future directions. The heterogeneous data would provide different views of the same patient to better support various clinical decisions (e.g. disease diagnosis and prognosis -3). HoweMany works have achieved great success in using a single modality to make a diagnosis or prognosis with deep learning methods -10. Howeet al [et al [et al [et al [et al [Several surveys have been published for medical multimodal fusion -15. Boehet al  reviewedl [et al  and Stahl [et al  and Lu el [et al  divided In this survey, we collected and reviewed 34 related works published within the last 5 years. All of them used deep learning methods to fuse image and non-image medical data for prognosis, diagnosis, or treatment prediction. This survey is organized in the following structure: 2.2.1.This survey only includes published studies (with peer-review) that fuse both image and non-image data to make a disease diagnosis or prognosis in the past five years. All of them used feature-level deep learning-based fusion methods for multimodal data. A total of 34 studies that satisfied these criteria are reviewed in this survey.2.2.A generalized workflow of collected studies is shown in Based on the stage of multimodal fusion, the fusion strategies can be divided into feature-level fusion and decision-level fusion , 15. Fea2.3.In this survey, multimodal fusion is applied to the disease diagnosis and prognosis. The disease diagnosis tasks include classifications such as disease severity, benign or malignant tumors, and regression of clinical scores. Prognosis tasks include survival prediction and treatment response prediction.After obtaining the multimodal representations, multi-layer perceptrons (MLP) were used by most of the reviewed studies to generate the prognosis or diagnosis results. The specific tasks of diagnosis and prognosis can be categorized into regression or classification tasks based on discrete or continuous outputs. To supervise the modal training, the cross-entropy loss is usually used for classification tasks, while the mean square error (MSE) is a popular choice for regression tasks. To evaluate the results, the area under the curve (AUC) of receiver operating characteristics (ROC), mean average precision (mAP), accuracy, F1-score, sensitivity, and specificity metrics are commonly used for classification, while the MSE is typically used for regression. However, although the survival prediction is treated as a time regression task or a classification task of long-term/short-term survival, the Cox proportional hazards loss function  is popul3.Due to multimodal heterogeneity, separate preprocessing and feature extraction methods/networks are required for different modalities to prepare unimodal features for fusion. As shown in 3.1.3.1.1.Pathology images analyze cells and tissues at a microscopic level, which is recognized as the ‘gold standard’ for cancer diagnosis . The 2D 3.1.2.Radiology imaging supports medical decisions by providing visible image contrasts inside the human body with radiant energy, including MRI, CT, positron emission tomography (PET), fMRI and x-ray, etc. To embed the intensity standardized 2D or 3D radiology images into feature representations with learning-based encoders -36, 87 o3.1.3.In addition to pathology and radiology images, some other kinds of medical images captured by optical color cameras are categorized as camera images; examples of these camera images include dermoscopic and clinical images for skin lesions , 45, end3.2.The non-image modalities contain lab test results and clinical features. Laboratory tests check a sample of blood, urine, or body tissues, access the cognition and psychological status of patients, and analyze genomic sequences, etc. Clinical features include demographic information and clinical reports. These modalities are also essential to diagnosis and prognosis in clinical practice. The non-image data on the reviewed works can be briefly divided into structured data and free-text data for different preprocessing and feature extraction methods.3.2.1.et al [Most of the clinical data and lab test results in the reviewed works are structured data and can be converted to feature vectors easily. In preprocessing, categorical clinical features were usually converted through one-hot encoding, while the numerical features were standardized , 34, 35.et al  used sofet al , 47, 67.et al , 24, andet al , 68.3.2.2.et al [Clinical reports capture clinicians’ impressions of diseases in the form of unstructured text. In order to deal with the free text data and extract informative features from the free-text, natural language processing techniques are implemented. For example, Chauhan et al  preparedet al . Then, tet al  model inet al  was usedet al  was trieet al  for textet al [et al [et al [et al [et al [et al [et al [After using the above modal-specific preprocessing and feature extraction methods, the unimodal representations could be converted to feature maps or feature vectors. For feature vectors, in order to learn more expressive features with expected dimensions, EI-Sappagh et al  used pril [et al  exploredl [et al  used thel [et al  replicatl [et al  deconvoll [et al  used bidl [et al  applied l [et al , 68, vecl [et al , 34, 35,l [et al .Unimodal feature extraction can be either unsupervised or supervised. Note that if the unimodal features are trained prior to fusion, it is possible to train the unimodal model with the maximum number of available samples of each modality for better unimodal model performance and hopefully better unimodal features to benfit the multimodal performance , 67, 84.4.et al [et al [Fusing the heterogeneous information from multimodal data to effectively boost prediction performance is a key pursuit and challenge in multimodal learning . Based oet al  implemenl [et al  showed tl [et al , 61 also4.1.et al [p-value > 0.05), while the element-wise summation and multiplication methods required less trainable parameters in the following FCN. After comparing the learned non-image features by FCN and the original non-image features, the former ones achieved superior performance. Meanwhile, the concatenation of the feature vectors outperformed the concatenation of logits from the unimodal data. Yan et al [et al [To combine different feature vectors, the common practice is to perform simple operations of concatenation, element-wise summation, and element-wise multiplication. These practices are parameter-free and flexible to use, but the element-wise summation and multiplication methods always require the feature vectors of different modalities to be converted into the same shape. Many early works used one of the simple operations to show that multimodal learning models outperforms unimodal models , 45, 87.et al  comparedan et al  investigl [et al  proposed4.2.et al [et al [et al [The subspace methods aim to learn an informative common subspace of multimodality. A popular strategy is to enhance the correlation or similarity of features from different modalities. Yao et al  proposedet al , they prl [et al  designedl [et al  used thel [et al  fused thl [et al , they foet al [et al [Another strategy in the subspace-based fusion method is to learn a complete representation subspace with the encoder-decoder structures. Ghosal et al  decoded l [et al  also use4.3.et al [et al [et al [et al [et al [et al [et al [et al [et al [et al [et al [Attention-based methods computed and incorporated the importance scores (attention scores) of multimodality features when performing aggregation. This progress simulated routine clinical practice. For example, the information from clinical reports of a patient may inform the clinicians to pay more attention to a certain region in an MRI image. Duanmu et al  built anl [et al  concatenl [et al  calculatl [et al  proposedl [et al  proposedl [et al  aggregatl [et al  and a bal [et al . Guan etl [et al  applied l [et al  in theirl [et al . In addil [et al  built a l [et al , and thel [et al  exploitel [et al  and finel [et al  used theet al [The above attention-based fusion methods rescaled features through complementary information from another modality, while Pölsterl et al  proposedet al .4.4.et al [et al [et al [The tensor-based fusion methods conducted outer products across multimodality feature vectors to form a higher order co-occurrence matrix. The high-order interactions tend to provide more predictive information beyond what those features can provide individually. For example, blood pressure rising is common when a person is doing high-pressure work, but it is dangerous if there are also symptoms of myocardial infarction and hyperlipidemia . Chen etet al  proposedet al  to combiet al  was addel [et al  not onlyl [et al . More rel [et al  followedl [et al  and exte4.5.et al [et al [A graph is a non-grid structure to catch the interactions between individual elements represented as nodes. For disease diagnosis and prognosis, nodes can represent the patients, while the graph edges contain the associations between these patients. Different from CNN-based representation, the constructed population graph updates the features for each patient by aggregating the features from the neighboring patients with similar features. To utilize complementary information in the non-imaging features, Parisot et al  proposedl [et al  built gr5.In the above sections, we reviewed recent studies using deep learning-based methods to fuse image and non-image modalities for disease prognosis and diagnosis. The feature-level fusion methods were categorized into operation-based, subspace-based, attention-based, tensor-based, and graph-based methods. The operation-based methods are intuitive and effective, but they might yield inferior performance when learning from complicated interactions of different modalities’ features. However, such approaches (e.g. concatenation) are still used to benchmark new fusion methods. Tensor-based methods represent a more explicit manner of fusing multimodal features, yet with an increased risk of overfitting. Attention-based methods not only fuse the multimodal features but compute the importance of inter- and intra-modal features. Subspace-based methods tend to learn a common space for different modalities. The current graph-based methods employ graph representation to aggregate the features by incorporating prior knowledge in building the graph structure. Note that these fusion methods are not exclusive to each other, since some studies combined multiple kinds of fusion methods to optimize the prediction results. Compared with decision-level fusion for the decision-level fusion, feature-level fusion may gain benefits from the interaction between multimodal features, while the decision-level fusion is more flexible for the combination of multimodalities and thus robust to modality missing problems.Although different fusion methods have different characteristics, how to select the optimal fusion strategy is still an open question in practice. There is no clue that a fusion method always performs the best. Currently, it is difficult to compare the performance of different fusion methods directly, since different studies were typically done on different datasets with different settings. Moreover, most of the prior studies did not use multiple datasets or external testing sets for evaluation. Therefore, more fair and comparative studies and benchmark datasets should be encouraged for multimodal learning in the medical field. Furthermore, the optimal fusion method might be task/data dependent. For example, the decision-level fusion might be more suitable for multimodality with less correlation. However, the theoretical analysis and evaluation metrics are not extensively researched. Some studies show that the fusion at different layers or levels can significantly influence the results , 84, 87.et al [et al [et al [et al [The reviewed studies showed that the performance of multimodal models typically surpassed the unimodal counterparts in the downstream tasks such as disease diagnosis or prognosis. On the other hand, some studies also mentioned that the models fused more modalities may not always perform better than those with fewer modalities. In other words, the fusion of some modalities may have no influence or negative influence on multimodal models , 40, 41.et al  used thel [et al  used outet al [et al [A concern in this field is data availability. Although deep learning is powerful in extracting a pattern from complex data, it requires a large amount of training data to fit a reasonable model. However, data scarcity is always a challenge in the healthcare area, the situation of the multimodal data is only worse. Over 50% of the reviewed studies used multimodal datasets containing less than 1,000 patients. To improve the model performance and robustness with limited data, the pre-trained networks  were used to visualize the activated region of images that were most relevant to the models’ outputs , 53, 67.et al  displayel [et al  used a pl [et al  used leal [et al  and Chenl [et al , Cheerlal [et al  and Braml [et al  displayel [et al  visualizl [et al  mentione6.This paper has surveyed the recent works of deep multimodal fusion methods using the image and non-image data in medical diagnosis, prognosis, and treatment prediction. The multimodal framework, multimodal medical data, and corresponding feature extraction were introduced, and the deep fusion methods were categorized and reviewed. From the prior works, multimodal data typically yielded superior performance as compared with the unimodal data. Integrating multimodal data with appropriate fusion methods could further improve the performance. On the other hand, there are still open questions to achieve a more generalizable and explainable model with limited and incomplete multimodal medical data. In the future, multimodal learning is expected to play an increasingly important role in precision medicine as a fully quantitative and trustworthy clinical decision support methodology.


Preterm birth is a worldwide health problem. After unsuccessful transvaginal cerclage, the transabdominal isthmo-cervical cerclage can be indicated. A laparoscopic approach has been described.A search was performed including the combination of: “((cerclage) AND (laparoscopy)) AND (pregnancy)”. A systematic review was performed to compare indications, outcomes, techniques, and safety.42 articles were found through database search. 30 articles were included for review. By reviewing the literature, the transabdominal cervico-isthmic laparoscopic cerclage is highly effective in selected patients with a history of refractory cervical insufficiency. This technique has a high neonatal survival rate when placed in preconceptional or post conceptional patients. Moreover, laparoscopic cervical cerclage is a safe procedure when laparoscopic expertise is present. A transvaginal cerclage is a procedure that places a stitch or tape within the cervix to mechanically close the cervix to prevent it from opening too early during pregnancy. However, if transvaginal cerclage fails, doctors may recommend a transabdominal isthmo-cervical cerclage using a laparoscopic approach. A systematic review analyzed 30 articles to compare the reasons for surgery, outcomes, techniques, and safety. The review suggests that this procedure is highly effective for certain patients with a history of refractory cervical insufficiency. It appears to be a safe technique with a high rate of survival for newborns and rare complications. Across 184 countries, the rate of preterm babies ranges from 5% to 18% of live births . Indicatet al.  and ScibThe research was performed using the PubMed database. Filters applied: in the last 5 years. A search was performed including the combination of the following words: “((cerclage) AND (laparoscopy)) AND (pregnancy)”. The search and selection criteria were restricted to the English language.The selection procedure followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) principles and is presented using a PRISMA flow chart . Recent The collection of data was done. Data were grouped depending on the type of clinical studies. Obstetrical outcomes and the differences in the surgical techniques were all reviewed.Inclusion criteria were hospitalized high risk women who underwent a laparoscopic cerclage preconceptionally or post conceptionally.-Gestational age at the moment of the cerclage.-Type of the tape.-Uterine manipulation.-Surgical technique.-Surgical complications.The operative technique and characteristics were as follows:-Mode of delivery.-Gestational age at the delivery.The pregnancy outcomes observed were as follows:Thirty studies were included in our review. The PRISMA flow chart is presented in et al. [et al. [Lesser et al.  and Scib [et al.  were theet al. had an important experience in laparoscopic cervical cerclage. They shared the outcomes of 121 pregnancies after a pre-pregnancy laparoscopic cervical cerclage in women at high risk for pre-term from 2007 to 2017 [et al. published a paper concerning their experience in laparoscopic transabdominal cerclage in 19 pregnant women at 6–11 weeks of gestation [et al. reported the obstetric outcomes of subsequent pregnancies in women who had a laparoscopic transabdominal cerclage left in situ [second pregnancy and 86% of women delivered after 34 weeks of gestation. On the other hand, the neonatal survival rate was 100% (3/3) in the third pregnancies, and 100% (3/3) of women delivered after 34 weeks of gestation.Ades  to 2017 . The peret al. who underwent a retrospective observational cohort study of patients operated on modified laparoscopic transabdominal cervical cerclage from 2003 to 2018 with a sample size of 299 pregnant women with a mean gestational age of 12.5 weeks [et al. in 2015, and it differs from the conventional laparoscopic cervical cerclage by the origin of the insertion of the tape – laterally to uterine vessels and above the uterosacral ligament. The different surgical techniques are detailed in The largest case series was reported by Chung .5 weeks . There wet al. in 2019: 24 women delivered by cesarean section, with 16/24 after 34 weeks and 21/24 women producing live births [However, there are few articles introducing the efficiency of laparoscopic cervical cerclage in twin pregnancy. The largest sample of twin pregnancy undergoing laparoscopic cervical cerclage was studied by Huang e births .et al. in 2021 [However, the outcomes of emergency laparoscopic cervical cerclage were introduced in one case series of 5 patients by Kavallaris  in 2021 . Patientet al. thoroughly studied the safety and beneficence of laparoscopic transabdominal cervical cerclage in their systematic review with meta-analysis [Moawad analysis , where tet al. [et al. [Laparoscopic cervical cerclage is a surgical approach suggested to prevent premature labor in high-risk women with a history of failed transvaginal cerclage, trachelectomy, or absent vaginal cervix. Hulshoff et al.  compared [et al.  showed tet al. compared in their meta-analysis 25 studies (1116 patients) on transabdominal cerclage placed by laparotomy to 15 studies (728 patients) on transabdominal cerclage performed by laparoscopy and they reported a higher neonatal survival rate in the laparoscopic group without difference in peroperative complications [A select cohort of women, with a history of second-trimester abortions or early preterm labor due to cervical insufficiency, should benefit from periconceptional counseling for laparoscopic cervical cerclage . These wet al. [et al. [et al. case series. On the other hand, the disadvantage of preconception cerclage is that pregnancy may either never occur or result in an early loss unrelated to cervical incompetence.The laparoscopic cervical cerclage can be provided before conception or after conception, most commonly during the first trimester of pregnancy. There is no cohort study dealing with the difference between the preconceptional and postconceptional laparoscopic cervical cerclage. A systematic review undergone by Tulandi et al. , evaluat [et al.  studied et al. experience [In the case of gravid women, using a uterine manipulator during laparoscopic cervical cerclage is not possible. In the modified LCC, four trocars were used with atraumatic forceps for uterine manipulation . Sponge perience . In precperience .et al. [et al. [et al. used Prolene n 1 in their laparoscopic cerclage (5–7). Shin et al. [et al. [et al. [Two types of tapes are described in the reviewed studies: The conventional Mersilene Tape and Prolene suture. Whittle et al.  were the [et al.  in choosn et al.  used Mer [et al.  where Pr [et al.  used Proet al. [et al. [Traditional laparoscopic cervical cerclage is based on a three-port laparoscopic approach with a fourth suprapubic assistant port. Four ports are preferable in gravid women to facilitate uterine manipulation. An incision is performed at the level of the utero-vesical fold in the visceral peritoneum and extended laterally to the broad ligaments. It is not necessary to carry out the bladder reflection systematically, while it is preferable in the case of previous cesarean sections. Most surgeons dissected the uterovesical and paravesical spaces and made a broad ligament window after identification of the ureters and uterine arteries. Although the suture may be inserted in either direction, there was no evidence that placing the suture from anterior to posterior has advantages more than the opposite direction. Some authors preferred the anterior to posterior direction for better visualization, and reduced risk of bowel injury and bladder erosions. Straight or straightened needles can be used during this procedure because they presented a more accurate direction of the suture. Furthermore, the suture is then passed at the level of the uterine isthmus medial to the uterine vessels. However, the tape is inserted laterally to the uterine vessels and above the ureters at the level of the uterine isthmus, above the uterosacral ligament in the modified laparoscopic cervical cerclage . This teet al.  describe [et al.  also deset al. [insitu and concluded a high neonatal survival rate after 34 weeks of gestation even in third pregnancies.Three different locations of the knot were described: anterior, posterior, and intravaginal knot. Anterior knots have the advantage of avoiding the risk of adhesions in the Douglas pouch, and can be easily removed in laparoscopy, but may increase the risk of erosion into the bladder. On the other hand, posterior knots can be removed via posterior colpotomy in case of pregnancy failure in the second trimester and this allows vaginal delivery. To avoid the unindicated cesarean section at term for removing the intracorporal cerclage knots, some authors described the intravaginal knot method to simplify knot removal . To sum et al.  conducteet al. [et al. case series of 121 interval cerclage [et al. [et al. [et al. [Multiple complications are described by reviewing the literature. Some complications were related to the laparoscopic surgery and others to the transabdominal cervical cerclage procedure. Although Moawad et al.  reportedcerclage . There w [et al.  was the  [et al.  did not  [et al.  publisheet al. [et al. case series [et al. study, 176 (85.9%) delivered successfully live births. 60 of 205 patients (29.2%) delivered before 37 weeks [et al. study [Moawad et al.  reportede series , where t37 weeks . FurtherTo our knowledge, this is a large and new systematic review exploring the surgical technique of the laparoscopic approach of abdominal cerclage with obstetrical outcomes. On the other hand, the small sample size in some of the included studies, their retrospective design, and the lack of standardized criteria for the technique, and timing of the operation represent the major limitations of this systematic review, thus making it difficult to conclude any convincing evidence on the management strategies. We also included case reports and case series, thus facing a higher risk of publication bias and decreasing the level of the evidence of our findings. Moreover, indications for delivery are not discussed in any study: patients with an indicated preterm labor  should be excluded.Future randomized cohort studies with a larger sample size are required to evaluate the best technique , the most efficient type of tape (Mersilene or Prolene), and the best timing for this procedure (preconception or first trimester) to have better obstetrical outcomes. However, these studies need significant statistical power. Furthermore, the beneficial outcomes of laparoscopic cervical cerclage may be a reason for medical laboratories and manufacturers to invest more in the production of resorbable tape based on native tissue. Moreover, further studies are needed to evaluate the efficiency of laparoscopic cervical cerclage in multiple pregnancies.Although the United Kingdom National Institute for Health and Care Excellence (NICE) classified laparoscopic cerclage as a procedure with limited evidence for success, multiple studies showed that transabdominal cervico-isthmic laparoscopic cerclage is highly effective in selected patients with a history of refractory cervical insufficiency. This technique has a high neonatal survival rate when placed in preconceptional or post conceptional patients. Moreover, laparoscopic cervical cerclage seems to be a safe procedure when the correct skill and laparoscopic expertise are present.After unsuccessful transvaginal cerclage, the transabdominal isthmo-cervical cerclage can be indicated in a selected high-risk patient. A laparoscopic approach has been described.The transabdominal cervico-isthmic laparoscopic cerclage is highly effective in selected patients with a history of refractory cervical insufficiency.This technique has a high neonatal survival rate when placed in preconceptional or post conceptional patients.Laparoscopic cervical cerclage is a safe procedure when laparoscopic expertise is present.


BMC Bioinformatics presented guidelines on long-read sequencing settings for structural variation (SV) calling, and benchmarked the performance of various SV calling tools, including NanoVar. In their simulation-based benchmarking, NanoVar was shown to perform poorly compared to other tools, mostly due to low SV recall rates. To investigate the causes for NanoVar's poor performance, we regenerated the simulation datasets (3× to 20×) as specified by Jiang et al. and performed benchmarking for NanoVar and Sniffles. Our results did not reflect the findings described by Jiang et al. In our analysis, NanoVar displayed more than three times the F1 scores and recall rates as reported in Jiang et al. across all sequencing coverages, indicating a previous underestimation of its performance. We also observed that NanoVar outperformed Sniffles in calling SVs with genotype concordance by more than 0.13 in F1 scores, which is contrary to the trend reported by Jiang et al. Besides, we identified multiple detrimental errors encountered during the analysis which were not addressed by Jiang et al. We hope that this commentary clarifies NanoVar's validity as a long-read SV caller and provides assurance to its users and the scientific community.A recent paper by Jiang et al. in  The benchmarking of structural variation (SV) calling tools provides end-users with vital information for comparing and selecting the optimal tool and settings for SV detection in their research. Hence, it is important to ensure that benchmark analyses are accurate and fair to faithfully reflect the benefits and drawbacks of each tool. In a recent paper by Jiang et al. , a benchhttps://github.com/SQLiu-youyou/The-commands-of-the-evaluation). For comparison, we have also included Sniffles [To investigate the poor performance of NanoVar in Jiang et al., we regenerated the long-read simulation datasets and benchmarked NanoVar in accordance to the methods stated in Jiang et al. (Sniffles  (describSniffles  v3.0.1)https://gWe also observed different performance results for Sniffles. While our F1 scores of Sniffles for SV calling by presence are broadly in agreement with Jiang et al., our F1 scores for SV calling by genotype concordance were substantially lower . The problem was resolved after we corrected the start coordinates of the file. The second error occurred when NanoVar was running on the simulated long-read BAM file produced by VISOR. The error happened because the read names of the simulated reads contained the comma  symbol, which resulted in a parsing error and prevented NanoVar from completing successfully. After removing the commas in the read names, NanoVar completed its run with no errors. As this was a necessary correction to obtain results from NanoVar, it is unclear how Jiang et al. had handled it and whether this influenced the results. The third error happened due to VCF file incompatibilities with Truvari for NanoVar and Sniffles. For NanoVar, an error was raised due to the presence of “>” or “.” symbols in the “SVLEN” field of some entries in the VCF file. These symbols were added by NanoVar to refine information on SV length, or nullify it for SVs with no lengths, respectively. When these symbols were omitted from the VCF file, Truvari ran successfully. For Sniffles, the error was caused by the “STRANDBIAS” string in the “FILTER” column of a few entries (< 50), and eliminating these entries resolved the problem. With the presentation of these VCF incompatibilities, it is plausible that there might be more nuances in the VCFs of NanoVar and Sniffles that impede an accurate assessment by Truvari. Taken together, we are uncertain how these fundamental errors were addressed by Jiang et al. and if they may have affected the results.During our analysis, we made some changes to certain output files within the protocol described by Jiang et al. However, these changes were made in order to rectify the errors that we encountered. As these errors were not mentioned by Jiang et al., they were unanticipated while following their protocol, and we are uncertain how Jiang et al. had resolved them to allow successful completion of their analysis. The first error we encountered happened during the long-read simulation step using VISOR  (v1.1) wIn conclusion, based on the Jiang et al. published materials, we were not able to entirely reproduce the results described by the authors’ benchmark. Indeed, our analysis performed on the same simulated datasets suggests an underestimation of NanoVar’s performance and an overestimation of Sniffles’ SV genotyping performance. We also encountered multiple errors while trying to replicate their analysis which might explain the discrepancy in results. We hope that the discussions provided here, as well as other studies –5, have


Obesity – a pandemic of the twenty-first century – is one of the greatest public health problems worldwide. Overweight and obesity affect nearly one in five children in the world and one in three in Europe . Recent No single cause is responsible for increased incidence of childhood obesity. It cannot be blamed on genetics factors or environment factors alone. In this Research Topic our contributors explore the mechanisms behind, linking intrauterine, postnatal, and early childhood metabolic environment to obesity and its complications , 5, 6.Nakhleh et al. revealed that class 1 obesity in children’s and adolescents (BMI ≥ 110% of the 95th percentile) was associated with higher prevalence and clustering of cardiometabolic risk factors.Rajamoorthi et al. highlighted the role of the environmental factors, including the globalization of the western diet and unhealthy lifestyle choices. In an elegant review they argued that starting from conception type and timing such exposures come into play impacting on the overall risk of obesity and future adverse health outcomes.Seget et al. as they documented that the prevalence of obesity is increasing among in children with diabetes mellitus type 1 (T1DM) and may influence the glycemic control.An important new observation was reported by Pixner et al. investigated LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects.On the other hand, Kącka et al. introduced novel markers of metabolic complications in obese T1DM and non-diabetic subjects.Sobek and Dąbrowski in article “Lifestyle intervention changes are crucial in the prevention and treatment of childhood obesity”.Analysis of the taste preferences and sensitivity of mothers and their children in the relation to excessive body weight of children is presented by Strączek et al. found that one-year dietary education resulted in significant improvements in body weight, waist, and hip circumference, WHtR and selected measured carbohydrate and lipid metabolism parameters with the exception of total cholesterol. The one-year dietary intervention did not have the same effect on the change in dietary habits in children and in their mothers.de Lamas et al. concluded that controlling obesity and cardiometabolic risk factors, especially insulin resistance and blood pressure in children during the prepubertal stage appears to be effective in prevention of pubertal metabolic syndrome.The assessment of childhood obesity comorbidities and risk of its complication is challenging and difficult. Artemniak-Wojtowicz et al. experimentally proved that weight reduction leads to significant decrease of circulating Th17 cells and improvement of lipid parameters. This significant reduction of proinflammatory Th17 cells is a promising finding suggesting that obesity-induced inflammation in children could be reversible.Maruszczak et al. described determinants of hyperglucagonemia in Pediatric Non-Alcoholic Fatty Liver Disease. Brunnert et al. revealed usefulness of the liver stiffness measurement in the evaluation of liver involvement in obese adolescents. Furdela et al. revealed that triglyceride glucose index, pediatric NAFLD fibrosis index, and triglyceride to high-density lipoprotein cholesterol ratio are a valuable combination of predictive markers of metabolically unhealthy phenotype in Ukrainian overweight/obese boys.One of the key problems in the development of obesity complications is the liver involvement. Liver abnormalities - collectively known as metabolic associated fatty liver disease is becoming a more prevalent clinical problem, in obese children and adolescents. Erazmus et al. in the article “Decreased level of soluble Receptor Activator of Nuclear Factor-κβ Ligand (sRANKL) in overweight and obese children”.Obesity can also associate with complications of calcium-phosphorus and bone metabolism regulation . That waKrajewska et al. confirmed that vitamin D has positive effect on metabolic profile in overweight and obese children, but the relationship between vitamin D and chemerin is not clear.Zembura and Matusik found that sarcopenic obesity is highly prevalent in children and adolescents and is associated with various adverse health outcomes including significant association with cardiometabolic outcomes, severity of non-alcoholic fatty liver disease (NAFLD), inflammation, and mental health. Findings of this review highlight the need for the development of a consensus regarding definition, standardized evaluation methods, and age and gender thresholds for sarcopenic obesity for different ethnicities in the pediatric population.Many factors influencing the development of obesity and its complications are still unknown. Future studies are needed to elucidate many questions and concerns raised by our contributors. Nevertheless, we do hope that readers will find our Research Topic informative and inspiring.AM, MW - writing draft of manuscript. AG, GT, EV - review. DM - final correction and approval.


We thank Dr. Elvira Alvarez Stehle  for her Although deviations from the original protocol were found in the PREDIMED trial, they do not affect the validation of the MEDAS questionnaire. Schröder et al.  did, in More recently, García-Conesa et al.  performeWe thus believe that the MEDAS questionnaire remains a useful and reliable tool for rapidly assessing adherence to the Mediterranean diet.


Cancer represents one of the most important general health problems of our day. The estimated incidence of new cases in 2020 was 19.3 million [Even when diagnosed at an early stage, cancer patients can experience a metastatic relapse. Gallicchio et al. estimated that, during a lifetime, the percentage of metastasisation can range from 30% for lung cancer to 72% for bladder cancer , even thAll of these improvements could not be reached without the translation of fundamental research into practical uses, ranging from the initial cellular level to the molecular level, and nowadays, we have a genetic understanding of cancerogenesis. Since the times of ancient Greece, multiple theories have been made about oncogenesis, and through ‘step by step’ discoveries, we have managed to learn how things work in the complex area of human biology, and new potentially valuable targets have emerged.One of the most important dreams of healthcare personnel—from research, clinical, or laboratory specialities—is to solve a little or big part of the complicated oncology puzzle, which could contribute to saving lives. Every small discovery could represent a big step in curing more people, such as by making more effective treatments available, diagnosing cancer earlier, or reducing the risk for cancer.This Special Issue, “Advances in Cancer Therapy from Research to Clinical Practice—Surgical, Molecular or Systemic Management of Cancer”, was initially designed to allow the potential authors to share their work in the very complicated world of oncology using a large amount of big data, which can be practice changing.The published articles covered a broad range of cancers, with the most important primary tumours being treated from a fundamental research or clinical practice point of view.For breast cancer, for example, Lisencu et al.  tried toMoreover, Mkrantonakis et al.  tried toThe molecular types of cancer are not a fundamental discovery without any clinical relevance. As shown by Szep et al. , multipaFor lung cancer patients, Ahn et al.  searchedIn melanoma cancer, rechallenging with BRAF inhibitors becomes an attractive option for multiple-relapse patients. The polyclonal theory of cancer remains an important element to be taken into consideration when we are in a difficult situation after standard therapy failure. Ksomidis et al.  showed sInflammation in cancer could be a target for immunomodulatory treatment, but could also represent an unfavourable factor for patients, being responsible for cancer progression. The combined peripheral neutrophil–platelet index seems to be an unfavourable predictor factor for overall survival in resectable oesophageal squamous cell carcinoma (ESCC) patients, as shown by Peng et al. . An absolute iron deficiency in colorectal cancer can impair not only the cardiac and respiratory functions, among others, but also the immune system’s defence. Deficient patients could be affected more and could present with more advanced disease–lymphatic invasion, as shown by Fagarasan et al. .For hepatocarcinoma, Chen et al.  showed tA new chemotherapy association or a new modality of drug delivery? Chioreanu et al.  tested aBody mass index can be a simple prognostic factor for prostate cancer, as shown in Popovici et al.’s article , due to Al-Gharaibeh et al.  analysedFor gynaecologic cancers, Obradovic et al.  investigMedicina by Simescu et al. [Multiple neoplasia represents a difficult pathology for an oncologist, as mentioned and developed in an article published in u et al. . Parathyu et al. . A rare u et al. .Cotorogea-Simion et al.  developeWe hope that the readers will find answers to their questions or read about a finding related to their scientific interest in our Special Issue.


Tomography is an open access journal dedicated to all aspects of imaging science from basic research to clinical applications and imaging trials. As Editor-in-Chief of Tomography it is my great pleasure to provide a summary of some of the most cited and viewed publications in Tomography in 2021–2022 to summarize the last year’s most relevant discoveries in clinical imaging.Tomography regarding AI and, in particular, in AI oncologic imaging applications. Takahashi et al. [Presently, artificial intelligence (AI) and patient radiation exposure likely represent the most relevant general research fields in clinical imaging. Several papers were published last year in i et al.  showed hi et al. . Park eti et al.  showed ti et al. . AI couli et al. . The usei et al. , which cTomography, Inaba et al. [Regarding occupational radiation protection, specific attention has been recently dedicated to the eye lens. The International Commission on Radiological Protection (ICRP) adopted the new recommendation of reducing the occupational eye lens dose limit from 150 mSv/year down to 20 mSv/year averaged over 5 years since cataracts can occur at lower radiation doses than those examined in previous epidemiological research. In a recent paper published in a et al.  showed hCOVID-19-related pneumonia still represents a main research topic in the radiological literature. In particular, imaging findings in long-COVID still represent a relevant field. Besutti et al.  showed tTomography still represents an important venue for radiology research especially in the most relevant topics of imaging science.In conclusion,


Staphylococcus aureus (LA-MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) are of growing concern. Staphylococcus schleiferi and coagulase-negative staphylococci occur as commensals of the skin and mucous membranes of animals. However, they have been implicated in a variety of infections and are frequently resistant to one or more antimicrobial classes. This Special Issue assembles a collection of original articles that shed further light on these fascinating bacteria and their potential impacts on both veterinary medicine and public health.Staphylococci figure prominently among those bacteria demonstrating antimicrobial resistance (AMR) and are thus responsible for significant problems concerning the treatment of the animals and humans that they infect. In particular, livestock-associated methicillin-resistant Staphylococcus pseudintermedius, the most common pathogen isolated from skin disease samples (particularly pyoderma) from dogs [S. pseudintermedius constitutes a growing concern. A range of novel potential treatments including vaccination and phage therapy are discussed.The review by Lynch and Helbig  providesrom dogs . The higmec (SCCmec) type and the antimicrobial susceptibility of staphylococci isolated from superficial pyoderma infections affecting dogs in Thailand. SCCmec type V was found in S. aureus, the S. intermedius group, S. lentus, S. xylosus, and S. arlettae, and although the authors do not state whether the coagulase-negative species were considered the primary bacterial pathogens in the cases from which they were isolated, the need to reduce environmental contamination and educate veterinary personnel and clients about the potential for the transmission to and from dogs of all resistant staphylococci is emphasized. The need for hygiene is supported by the results of another recent longitudinal study of MRSP-infected dogs conducted by Frosini et al. [S. pseudintermedius isolates that showed MICs < 2 µg/ml, an interesting finding in light of the publication by Wegener et al. [Chanayat et al.  investigi et al. , in whici et al. , includer et al.  suggestiS. pseudintermedius isolates causing superficial pyoderma in Taiwanese dogs, Lai et al. [S. pseudintermedius from their pets. Although no significant association was found, high odds ratios were obtained for “keeping three or more dogs” and “dogs can lick the owner’s face”, suggesting support for recent publications describing the potential for S. pseudintermedius infections in human hosts [As well as characterizing i et al.  also exaan hosts ,8.Certain foods and food production systems may present a pathway for the transmission of MRSA to humans. Benrabia et al.  detectedStaphylococcus aureus is still the leading cause of bovine mastitis in many countries. Rusenova et al. [S. aureus in Bulgaria. The discrepancies detected for some isolates are concerning and, as recommended by the authors, highlight the need for isolates to be thoroughly characterized.a et al.  comparedS. aureus [Biofilm production is considered an important virulence factor for . aureus  and coag. aureus  showed tThe diverse articles contained in this Special Issue constitute a valuable contribution to our understanding of staphylococcal infection in both farm and companion animals.


Plants (ISSN 2223-7747) presents a comprehensive update of the current progress in the field. It includes a total of 38 articles, 29 original research papers, 5 reviews, 2 conference reports and 2 communications, encompassing almost all areas of research and applications related to the aquatic monocotyledonous plants duckweeds. The content of this Special Issue reflects the diversity of the duckweed community well in terms of the focal areas of research  using the method of tubulin-gene-based polymorphism . Whereas several distinct clones were identified within the populations of each pond in the case of L. minor, S. polyrhiza clones only showed genetic differences between the ponds [atpF-atpH and psbK-psbI), Chen et al. [Lemna aequinoctialis did not form a uniform taxon, which might be a hint for the existence of hybrids. The same plastidic markers for barcoding were used by Yosef et al. [L. gibba G3 was shown to be tetraploid [The family Lemnaceae was circumscribed by Ivan Martinov 1771–1833) as early as 1820. Therefore, the valid name of the family is Lemnaceae Martinov . With th71–1833 acf. also ). This pcf. also  used fivariation . This alhe ponds . Using pn et al.  identifif et al. , identiff et al.  summariztraploid . This muWater pollution and meeting the ever-increasing clean water demands are interconnected problems that our modern society must tackle. Duckweeds have long been considered as potent candidates for wastewater management. As reviewed by Zhou et al. , these fSix case studies examined the performance and pitfalls of duckweed-based wastewater remediation systems. Using multi-tiered indoor bioreactors, Coughlan et al.  studied 3− or NH4+ as inorganic nitrogen sources was general or rather species-specific amongst Lemnaceae. In addition, they provided insights to the complex regulation of nitrogen assimilation in these plants by reporting the molecular structure and differential expression of several key enzymes in response to different inorganic nitrogen sources. Nitrogen availability is not only crucial in the plants’ nutritional status, but may also modulate responses to other stressors, such as the presence of heavy metals. In their study, Kishchenko et al. [4+ could mitigate manganese toxicity in S. polyrhiza, including the interactions between Mn availability and the transcription of ammonium transporters. Besides remediation, metal accumulation may also gain significance when future duckweed-based feed and food production is considered. Accordingly, Pakdee et al. [A series of studies addressed basic physiological processes that make duckweeds efficient in water remediation and waste valorisation. Zhou et al. , by studo et al.  focused e et al.  identifie et al.  comparedL. minor and Wolffiella hyalina in an indoor experiment under the influence of different nitrate-to-ammonium ratios. The best results were obtained in a 50% diluted N medium with a nitrate-N to ammonium-N ratio of 3:1. In an additional set of experiments, the influence of light intensity and light source spectrum was investigated in a “small-scale, re-circulating indoor vertical farm” [Wolffia species in space applications. As the authors pointed out, the world’s smallest plants are promising candidates to be incorporated into bioregenerative life support systems in long-term space missions, and they are able to recycle water and oxygen for astronauts while also providing them fresh vegetable biomass.Application of duckweed on an industrial or commercial scale requires the production of large amounts of biomass. This can be attained either by using very large water surface areas or by using a large number of smaller facilities in a modular arrangement. Wastewater cleaning with typically very high volumes of liquid waste might be preferentially carried out outdoors in large ponds or waterways —althoughal farm”  providinal farm” ). The saal farm” . Romano al farm”  discusseLemna) have very high growth rates combined with unusually high levels of zeaxanthin, which is important for human nutrition. Moreover, Lemna plants can respond to elevated CO2 concentrations with increasing growth rates. It has been known for a long time that under stress conditions, the protein content of duckweeds decreases as strongly as the starch content increases. The accumulation of starch in a large number of duckweed species under nutrient-limited cultivation conditions  has been shown [Lemna turionifera under sulphur limitation in the study of Wang et al. [A group from Italy substituted different amounts of the standard feed of rainbow trout on the protein basis and reported that 20% substitution did not have any negative effects on the fish, but 28% substitution did show effects such as reduced fish body weight and a few other parameters . Demmig-en shown . Starch g et al. .Rhodobacter, changes after transfer from conditions in nature to nutrient-deficient conditions. Some herbivores feed on duckweeds, e.g., on S. polyrhiza. Schaefer and Xu [S. polyrhiza tested did not differ in their resistance toward the herbivore. However, after outdoor inoculation with microbiota associated with the same plant species, altered herbivory tolerance was observed in a genotype-specific manner.The interaction of duckweeds with microorganisms, especially plant-growth-promoting bacteria, can result in enhanced plant growth . The ider and Xu  quantifiWolffia arrhiza treated with brassinolide and brassinazole, a synthetic brassinosteroid inhibitor. Kozlova and Levin [L. minor to a fish steroid, 17β-Estradiol, that has been released at a large scale by intensive fish farms, and they found growth-promoting effects.Duckweeds are ideal for studying hormonal effects in plants, as they can be cultured axenically and take up substances directly into the shoot. As a vivid example of this traditional role, Chmur and Bajguz  analysednd Levin , on the Besides plant physiology research, bioindication of pollutants is another classical field of duckweed applications. Microplastics are emerging contaminants and, as such, their potential risks need to be explored urgently. Two studies aimed to fill this knowledge gap: Rozman and Kalčíková  tested iThe present Special Issue gives an update on the state of the art of duckweed research and applications and, together with the two previous Special Issues on this topic ,53, demo


Dura est manus cirurgi, sed sanans.The hand of the surgeon is hard, but healing.Walter Map, (1135–1210), British writerSince minimally invasive surgery (MIS) such as video-assisted thoracoscopic surgery (VATS) was introduced over 2 decades ago, it has revolutionized the thoracic surgery field. MIS can offer many advantages such as reduced anaesthesia and hospitalization time, less tissue damage and pain, decreased intraoperative blood loss, lower risk of postoperative infection and complications, better cosmetic outcome and faster recovery compared to traditional open technique . When coHowever, VATS is definitely not a panacea and it actually has a number of technical drawbacks , 2, 4. OAnother significant limitation of MIS is the lack of tactile sense during tool—tissue interaction that severely impairs the surgeon’s ability to control the applied forces—and thus can cause unintentional damage or additional trauma to healthy tissues . TactileRecent advances and more widespread application of computational tomography (CT) including the use of low-dose high-resolution CT protocols have allowed for the early detection of small pulmonary nodules (PNs) and improved early-stage lung cancer screening , 6. VATSet al. [In this article, Messina et al.  explore et al. . In thiset al. . The autet al. .et al. [et al. [The use of IUS for detecting lung nodules is not novel! Almost 2 decades ago, Santambrogio et al.  utilized [et al.  utilized [et al. .et al.’s study can overcome this disadvantage and have been shown to be very accurate locating small PNs of 20 mm or less at depths of up to 15 mm [However, in contrast to lung nodules, GGOs are small areas of hazy increased attenuation on CT that do not obscure underlying bronchial structures or vascular markings and often do not present with a solid, firm component. And herewith is their main difference compared to PNs, for their detection even with open palpation is extremely challenging! Nevertheless, high-frequency ultrasound probes such as the one used in Messina to 15 mm , 9.et al. can be considered a glimpse into the future because the authors, by utilizing high frequency IUS, were now able to not only quite effectively locate the GGOs but also to accurately define and characterize/describe them. Therefore, one may safely expect that as ultrasound resolution and technique improve further its applicability in thoracic surgery will probably become more widespread and thus the ‘manus cirurgi’ will end up replaced by ultrasound to effectuate ‘sānantem’!Consequently, this report by Messina


Agnaou et al., RSC Adv., 2023, 13, 8015–8024, https://doi.org/10.1039/d3ra00485f.Correction for ‘New silicon substituted BiMeVO The authors regret that the name of one of the authors (A. Agnaou) was shown incorrectly in the original article. The corrected author list is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Nutrients [We have read the article entitled “The effect of goat-milk-based infant formulas on growth and safety parameters: a systematic review and meta-analysis” by Jankiewicz et al. published in utrients .sn-2 palmitic acid), while the other formula tested by Xu et al. [We acknowledge the relevance of this systematic review due to the increasing number of goat milk formulas (GMFs) available worldwide. Only two GMFs have been clinically evaluated to help caregivers and healthcare professionals make an informed choice when selecting a nutritional product. However, the article did not present key compositional differences between the two GMFs, which may affect nutritional and health outcomes beyond infant growth. One formula evaluated by Grant et al.  and Zhouu et al.  and He eu et al.  is made s2-casein as the protein linked to less protein aggregation in goat milk when it should refer to a lower level of αs1-casein. The risk of the bias assessment process for D1 (randomization process) is not clearly explained, and, based on information provided in all publications, it is unclear why the publication of Zhou et al. [In addition, a few issues appear unclear and should be corrected. The introduction refers to a higher level of αu et al.  was asseu et al.   was used. And the reference to two ongoing trials should also indicate which formula is used, as the nutritional and health outcomes in these two studies are only valid for the formula under investigation. For example, it is well known that for allergy outcomes, clinical data and efficacy in allergy prevention or treatment of hydrolysed formulas cannot be generalised to any hydrolysed formulas. Therefore, the same would apply to the allergy outcome results from the GIraFFE study (NCT04599946).Importantly, a statement about the conflicts of interest from the GMF company authors is missing.


Periodontitis is an inflammatory disease that affects the supporting tissues of teeth, the effects of excess of nitric oxide, may contribute to the symptoms of periodontitis. To determine the serum nitric oxide concentration in generalized chronic and aggressive periodontitis patients and to compare it with a healthy subject group from the Mexican population.Clínica de Posgrado de Periodoncia of the Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, México. Patients with clinical features of generalized chronic periodontitis , generalized aggressive periodontitis , and a group of healthy subjects  were included in the study. Informed consent was obtained from each subject, and serum nitric oxide concentration was measured by an enzyme-linked immunosorbent assay. A case and control study was performed. Sixty-nine individuals were recruited from the  Nitric oxide concentration in the study groups was greater in the GCP group (462.57 ± 16.57 µmol/L) than in the GAP group (433.84 ± 18.61 µmol/L) and the HS group (422.46 ± 12.07 µmol/L). A comparison using Student’s t-test (one-tailed) between healthy subjects and generalized chronic periodontitis showed borderline significance (p<0.04), whereas no significant differences were observed in HS and GAP groups, with a p-value of 0.64, and the GAP vs. GCP p-value was 0.33. The serum nitric oxide concentration observed in the present study suggests that nitric oxide plays a major role in the inflammatory process, which cannot necessarily be linked to the severity of the disease and periodontal tissue destruction. It shows an accelerated destruction of periodontal tissues with alveolar bone loss in otherwise clinically healthy subjects Nitric oxide is now accepted as a prevalent biological mediator in many organisms. In mammals, nitric oxide is involved in several intercellular and intracellular activities, such as blood vessel dilation, neuronal intermediary, cytotoxicity, regulation of the cardiac rhythm and cellular respiration activities Nitric oxide originates from a cluster of isoenzymes denominated nitric oxide synthases (NOS), which exist as three specific isoforms: endothelial NOS (eNOS), neural NOS (bNOS), and inducible NOS (iNOS). eNOS and bNOS deliver a limited amount of nitric oxide for a brief time following receptor stimulation. In contrast, iNOS is expressed due to proinflammatory mechanisms and generates a high volume of nitric oxide for longer periods.The progression of chronic harmful inflammation of the periodontium may be a disrupted process. The effects of spare nitric oxide in the gingival mucosal tissue could contribute to the progression of the most frequent clinical signs of periodontitis in humans. The vasodilatory action of nitric oxide could be related to gingival redness, and gingival swelling may be provoked by the increase in the permeability of blood vessels induced by nitric oxide. The enlarged propensity of gingival tissue to bleed on probing may demonstrate the inhibitory mechanism of nitric oxide on platelet aggregation and the inhibitory activity of nitric oxide on adhesion A high concentration of nitric oxide produced locally is crucial in nonspecific host defense because of its cytotoxic activity against several organisms, as well as tumor cells. Nitric oxide released by eNOS plays a role in maintaining periodontal vascular perfusion et al., were the first to show that the salivary nitric oxide concentration is associated with the severity of periodontitis, allowing to differentiate between moderate and advanced chronic periodontitis. They proposed that NOS inhibitors could be valuable in the treatment of periodontal disease Reher, This study aimed to measure the serum nitric oxide concentration in patients with generalized chronic and aggressive periodontitis and compare it with that of healthy subjects.Clínica de Posgrado de Periodoncia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara. Patients with clinical features of generalized chronic and aggressive periodontitis and healthy subjects were included in the study Sixty-nine individuals were recruited from the Medical and dental records were taken from all participants. None had a history of current smoking or systemic disease; or had received antibiotic, immunomodulatory, or anti-inflammatory drugs; or had received periodontal treatment within the previous six months. Pregnant and breastfeeding women were excluded from the study. The purpose of the study was explained fully to each participant before they were accepted into the study.Institutional ethics review committee approval for the study was obtained (CI-01715), and informed consent was obtained from each participant in accordance with the 2013 Helsinki Declaration.® ) by a single researcher.Clinical parameters  were measured at six sites per tooth  using a periodontal probe . The amount of destruction was consistent with local factors, including subjects with ≥30% of sites with pockets, including a CAL of ≥5 mm and PD of ≥6 mm with radiographic evidence of alveolar bone loss This study group comprised 11 patients ; they had a family history of ≥1 family member with severe periodontal damage. They showed radiographic evidence of severe alveolar bone loss and clinical attachment loss minimum of ≥5 mm in eight or more teeth, at least three of which were not central incisors or first molars, and PD ≥6 mm (8).This study group included 39 participants  without history of systemic diseases or tobacco smoking and health status  Venous blood from patients and healthy subjects was collected, and serum samples were separated by centrifugation at 900g (10 minutes). The obtained samples were stored and frozen immediately at -70 °C until analysis. Serum nitric oxide levels were measured by enzyme-linked immunosorbent assay, ELISA . Optical density was measured in a microplate reader set to 450 nm with wavelength correction at 540 nm. The concentrations were calculated with the standard curve included in each assay kit and were expressed as µmol/L.Clinical and demographic parameters in the study groups were determined by Student’s t-test and Fisher’s exact test, respectively. The nitric oxide concentration was compared among the three groups using Student’s t-test. Significance was considered at a p value <0.05.In terms of age, a difference was observed: the HS group was younger than the GCP group (p<0.0001); also, the comparison of the GCP vs. GAP groups showed a significant difference (p<0.0001). In terms of sex, women predominated in all the study groups and did not exhibit differences.Among the periodontal clinical parameters, PD demonstrated statistical significance between the HS vs. GCP and HS vs. GAP groups (p<0.0001) in both cases when using Student’s t test (table 1).The serum nitric oxide concentrations are presented as the means ± standard deviations. The nitric oxide concentration did not differ significantly between the GAP group (433.84 ± 18.61 µmol/L) and the GCP group (462.57 ± 16.57 µmol/L) or between the GAP group and the HS group (422.46 ± 12.07 µmol/L). The comparative analysis was only significant between GCP and HS, but it showed borderline significance (p=0.04) .et al. et al. et al. The participation of nitric oxide in physiological actions depends on its origin, duration, and concentration et al. (17), and Wang, et al. et al. et al., reported higher levels of salivary nitric oxide in periodontally healthy subjects than in chronic periodontitis patients Contrary to Schmidt, et al. et al. ,In contrast to Reher, et al. et al. The differences in nitric oxide concentration in GCP vs. HS could be explained by the fact that nitric oxide participates as a biomessenger of bone loss induced by inflammation et al. et al. (26), noted that high nitric oxide production by endothelial cells in bone plays a physiological role by regulating the activity of osteoclasts, which probably limited the alveolar bone damage observed in the GCP group in the present study.With respect to the origin of nitric oxide, McCarty, et al. et al. et al. et al. et al. in vitro and stimulates osteoblast apoptosis On the other hand, Daghigh, et al. et al. et al. et al. et al. The involvement of nitric oxide and NOS in apposition and bone resorption is controversial. Fukada, et al. ,Additionally, MacIntyre, Our results allow us to infer that iNOS and eNOS, along with other mechanisms or related metabolic pathways, probably account for the severity of alveolar bone loss in periodontitis. It is likely that the pathways that activate NOS, which produces nitric oxide, differ between generalized aggressive and chronic periodontitis, and in healthy subjects; the difference in pathways is probably related to the damage observed in these patients. Additionally, time-dependent effects and concentrations could participate in the phenotypic consequences of periodontitis.Supplementary studies are required to address the role of nitric oxide in periodontitis. The higher serum nitric oxide concentration in patients in the GCP group suggests that nitric oxide plays a major and selective role in the inflammatory process and that the nitric oxide concentration and origin are probably not related to the severity of the disease.


Philosophical Transactions published G. I. Taylor’s seminal paper on the stability of what we now call Taylor–Couette flow. In the century since the paper was published, Taylor’s ground-breaking linear stability analysis of fluid flow between two rotating cylinders has had an enormous impact on the field of fluid mechanics. The paper’s influence has extended to general rotating flows, geophysical flows and astrophysical flows, not to mention its significance in firmly establishing several foundational concepts in fluid mechanics that are now broadly accepted. This two-part issue includes review articles and research articles spanning a broad range of contemporary research areas, all rooted in Taylor’s landmark paper.In 1923, the Philosophical Transactions paper (part 2)’.This article is part of the theme issue ‘Taylor–Couette and related flows on the centennial of Taylor’s seminal  Philosophical Transactions A a century ago, G. I. Taylor connected theory and experiment in his ground-breaking investigation of flow between differentially rotating concentric cylinders [In a remarkable paper published in the ylinders . The papylinders , which aTaylor’s 1923 paper has inspired several generations of researchers in fields ranging from nonlinear dynamics to astrophysics. Not only does Taylor–Couette flow display remarkable vortical patterns that are easily generated and visualized, it is a test bed for studies probing fundamental aspects of fluid flow as well as practical engineering applications.Philosophical Transactions.Part 1 of this two-part theme issue explored contemporary topics related to Taylor–Couette flow including turbulent, convective and two-phase flows as well as extensions to magnetohydrodynamic, ferrofluidic and viscoelastic flows and flow geometries that are closely related to the Taylor–Couette problem –18. Partet al. [et al. [et al. [This issue starts with several papers that consider much the same problem as Taylor did, but with an emphasis on turbulence rather than the linear onset of instability. Feldmann et al.  review t [et al.  present  [et al.  conduct et al. [et al. [et al. [As in Part 1, we have several papers on the interaction of Taylor–Couette flow with convection, but with one crucial difference. The papers in Part 1 imposed a temperature gradient in the cylindrically radial direction, which corresponds to a radial force field playing a role like that of gravity. By contrast, the papers here impose gradients in the axial direction, matching gravity in a typical laboratory setting. Lopez et al.  review T [et al. , who pre [et al.  impose uJi & Goodman  present et al. [et al. [et al. [As was the case in Part 1, the Taylor–Couette problem can be extended by considering fluids that are more complex than Newtonian fluids. Bai et al.  and Moaz [et al.  both pre [et al.  consider [et al.  conduct  [et al.  present et al. [et al. [Finally, and again as in Part 1, there are a variety of systems and geometries that are not strictly Taylor–Couette flows as such, but are nevertheless closely related. Nagata  presentset al.  consider [et al.  numericaPhilosophical Transactions. It is clear that the study of Taylor–Couette flow will continue to provide a basis for a broad range of important and fundamental research topics for many decades to come.This two-part theme issue is a fitting tribute to celebrate the centennial of Taylor’s foundational paper in the


Da increased while the slip parameters The modeling and analysis of hybrid nanofluid has much importance in industrial sector where entropy optimization is the key factor in different processes. This mechanism is also used in medical industry, where it can be used for separation of blood cells  by centrifuge process, treating cancers, and drug transport. In light of this importance, current study is focused on mathematical modeling and analysis of blood based hybrid nanofluid between rotating disks with various shapes of nanoparticles. The shape factors are taken into account with Hamilton–Crosser model as spherical, brick, cylinder and platelet in the current scenario, with special reference to entropy optimization. In order to solve modeled nonlinear and non-dimensional system, optimal homotopy analysis approach is utilized through Wolfram MATHEMATICA 11.3 software. Error estimation and convergence analysis confirms that obtained semi-analytical solutions are valid and reliable. Velocity, temperature and concentration profiles are analyzed against important fluid parameters. Fluid velocity decreased in all directions when unsteady parameter  Subray et al.2 comparatively analyzed the flow of a nano and hybrid nanofluid for brick, blade and laminar shaped nanoparticles. Li and You3 simulated the flow of a water-based hybrid nanofluid over a stretching sheet with various shapes of copper and alumina nanoparticles. Akbar et al.4 studied the Maxwell nanofluid flow over a linearly stretched surface. Analysis on cross flow of hybrid nanofluid with numerous nanoparticle shapes is performed by Ramesh5. Study on a rate type nanofluid over a magnetized stretching sheet is performed by Liu et al.6. Dinarvand and Rostami7 studied squeezing of hybrid nanofluid with variable shapes. Ghobadi and Hassankolaei8 numerically simulated the hybrid nanofluid on cylinder with different shape factors. Chung et al.9 analyzed three dimensional hybrid nanofluid flow with heat source/sink. Gholinia et al.10 explored nanofluid with varying shapes of titanium oxide and alumina nanoparticles. Nasir et al.11 studied hybrid nanofluid flow over a Darcy-Forchheimer porous surface. Waqas et al.12 explored different shapes of gold nanoparticles in Sisko fluid. Li et al.13 studied slip effects on a nanofluid flow over stretching sheet.Hybrid nanofluids are colloidal mixtures containing two type of nanoparticles mixed in a single base fluid. These fluids are useful in applications where heat and mass transfer enhancement is required to obtain more efficient and effective systems. Hybrid nanofluids especially with different shapes of nanoparticles can further improve the heat transfer effects due to which their study has gained interest of many researchers. Kashi’e et al.14 investigated Williamson nanofluid with swimming gyrotactic microorganisms. Khalaf et al.15 improved the heat transfer effects in a nanofluid with porous media. Chu et al.16 studied heat transfer of a hybrid nanofluid in a microchannel. Ahmad et al.17 analyzed the bio-convective flow of a gyrotactic microbes based nanofluid flow over a non-linearly stretched sheet and passing through a porous medium. Muhammad et al.18 investigated the Darcy-Forchheimer porous medium flow of a carbon nanotubes based nanofluid. Li et al.19 enhanced the heat transfer properties of the time-dependent viscous fluid flow. Gul et al.20 analyzed heat transfer in a hybrid nanofluid flow in a porous chamber. Panigrahi et al.21 numerically simulated the effects of porous media on MHD flow of a Casson nanofluid using Runge-Kutta method with shooting technique. Babu et al.22 simulated the heat and mass transfer effects in a nanofluid flow over a wedge. Nasir et al.23 enhanced the heat transport properties in stagnation point flow of a hybrid nanofluid. Esfe et al.24 studied the impact of porous medium on three different types of convective transfer through heat. Recently, Prasannakumara25 investigated the influence of porous media on methanol and NaAlg based nanofluid flow through Tiwari-Das model. Ragupathi et al. in26 explored radiative Casson nanofluid over a radially stretching and rotating disk.Increase in energy generation gathered much attention in last decade. Bhatti et al.27 sought out to improve the thermal transport of two types of nanofluids (mono and hybrid) passing over an inclined sheet with heat source/sink effects. Nasir et al.28analyzed entropy generation in ethylene glycol and water based nanofluid. Yaseen et al.29 investigated the flow of a water based hybrid nanofluid past a moving convective heated surface with heat source/sink, velocity slip and non-linear thermal radiation. Sajid et al. in30 investigated a Cross non-Newtonian tetra hybrid nanofluid flow in a stenosed artery. Sulochana and Kumar31 enhanced the rate of of heat transfer with heat source and sink in a mono and hybrid nanofluid over a stretching surface. Chu et al.32 analyzed Jeffrey nanofluid with chemical reaction between two disks. Chamkha et al.33 numerically analyzed the copper-alumina hybrid nanofluid flow with water as base fluid inside a partially heated square cavity under heat generation and absorption effects. Gorla et al.34 investigated heat source and sink effects on a hybrid nanofluid flow in a porous cavity. In a recent study, Yasir et al.35 applied a non-uniform heat source/sink in an ethylene glycol based hybrid nanofluid with Hamilton-Crosser model. Saleh et al.36 simulated effects of heat generation and absorption on a Maxwell hybrid nanofluid with MHD effects. Dinarvand et al.37 performed a numerical investigation on squeezing flow of a water based hybrid nanofluid between two collateral sheets influenced by heat generation and absorption.Many applications of rotating disks involve heat generation and absorption phenomena in order to perform the task optimally. It can either require higher temperatures or extremely lower temperatures depending on the phenomena under consideration. For instance, in order to separate platelets and other components from blood rotation, an ambient temperature must be maintained in order to achieve the desired results. Different studies in literature have taken heat source/sink into account. Ali et al.38 attempted to minimize the entropy generation in membrane reactor of methanol synthesis with various geometries by using optimal control theory and linear programming. Khan et al.39 investigated the entropy minimization in a non-linear thermal radiative flow of hybrid nanofluid with water as a base fluid. Obalalu et al.40 minimized the entropy generation in a Casson nanofluid flow over a stretching Riga plate and non-Darcy porous medium. Nasir et al.41 optimized entropy generation in a Maxwell nanofluid flow. Li et al.42 simulated entropy generation in stagnation point flow of Carreau nanofluid. Munawar et al. in43 investigated the entropy minimization of a hybrid nanofluid flow inside a corrugated triangular annulus with magnetic effects and free convection. Khan et al.44 simulated entropy generation in a viscous nanofluid with second order velocity slip. Ibrahim et al.45 analyzed entropy generation in a nanofluid flow with twisted porous objects. Mabood et al.46 minimized the entropy generation in a Jeffery nanofluid boundary layer flow over a permeable stretching sheet with non-linear thermal radiation and activation energy. Acharya et al.47 investigated the entropy generation in a ferrous oxide and graphene oxide hybrid nanofluid over an unsteady spinning disk with slip effects.Entropy generation is the useful energy dissipated in the environment and it results in reduced efficiency of engineering systems and biological processes. Many studies in recent years are focused on entropy minimization to provide best possible conditions and obtain maximum output as a result. Li et al.The focus of current study is entropy analysis, and modeling of heat and mass transfer in a blood based unsteady hybrid nanofluid with radium and alumina nanoparticles having various shapes including spherical, brick, platelet and cylindrical through Hamilton-Crosser model. The nanoparticles of current study are important in enhancing heat and mass transfer properties of blood which is useful in many applications of medical industry including drug transport, cancer treatment and centrifuging blood to obtain its components . The flow is simulated with slip boundary conditions and fluid rotation between double rotating disks. The flow is also influenced by magnetic field, porous medium and heat sink/source. Using appropriate transforms modeled equations are converted to system of nonlinear ODEs. The solution method adopted is a semi-analytical approach namely, homotopy analysis method (HAM). The series form solution obtained with this method are validated through mean square errors and convergence table. Moreover, solutions obtained through HAM are also compared with Runge-Kutta 4th order solutions to provide further validation of results. The nanofluid flow in radial axial and tangential directions is graphically analyzed. Fluid temperature and concentration is simulated against pertinent fluid parameters. Entropy generation is presented numerically and graphically. In rest of the article, mathematical formulation is given in Section “Rd and alumina 48The flow geometry consists of double rotating disks with cylindrical coordinated mentclass2pt{minimu, v, w) are the velocities of fluid in r, z directions, respectively. T is the temperature and C is the concentration of fluid. L is the slip distance. t having unit (s) and b having the unit 49 which also considers the shape factor of the nanoparticles involved. The thermo-physical quantities in this case are given belowBehavior of nanofluids vary depending on base fluid and nanoparticles taken into account. There are many models in literature that characterize various properties of nanofluids. The hybrid nanofluid model considered in this study is the Hamilton-Crosser model50hnf’ presents the quantities of hybrid nanofluid,’f’ presents the quantities of base fluid whereas ’Rd’ and ’Al’ presents the radium and alumina quantities, respectively.The thermal conductivity for the current phenomena ismentclass2pt{minim50The hybrid nanofluid thermal diffusivity is given as50The electrical conductivity of hybrid nanofluid containing radium and alumina nanoparticles is50The kinematic viscosity is given as50The density and heat capacity of hybrid nanofluid is53Da is the Darcy number, Pr is the Prandtl number, M is the magnetic interaction parameter and We non-dimensionalize the system of partial differential equations given in Eqs. –4) by i by i4) b54At the disk wall use Eq.  in Eq. , th, th5833\The convergence of series solution is determined through entclass1pt{minimaThe hybrid nanofluid flow between two rotating disks is simulated for various fluid parameters and physical interpretations are drawn in this section for velocity, temperature and concentration profiles. Parameters of physical interest like entropy generation, Bejan number, skin friction, Nusselt number and Sherwood number are also discussed in detail.Da decreases the radial and axial velocity.Larger Darcy number results in increased viscous forces among fluid layers that causes resistance to fluid flow in radial and axial directions. Increase in stretching parameters u-direction and decreasing the rotation of disk in Radial, axial and tangential velocities are presented against pertinent fluid parameters in Figs. Pr increases the fluid temperature due to elevated thermal diffusivity. Increase in heat source Change in fluid temperature is observed in Figs. Concentration of blood nanofluid against unsteady parameter M in Fig. M increases the resistance in fluid flow increases due to the Lorentz forces and disorderedness of system increases. Increase in volume fraction of radium and alumina increases entropy while Bejan number behaves oppositely  with increase in unsteady parameter Both stretching parameters Increase in slip parameter Pr and heat source Temperature increases with higher values of Prandtl number Overall temperature of the fluid is highest in case of brick shaped nanoparticles whereas platelet shape nanoparticles result in lowest fluid temperature.Concentration of blood hybrid nanofluid increases with higher values of unsteady parameter M, volume fractions Br and Reynolds number Re whereas Bejan number behaves in contrast.Entropy generation increases with increase in magnetic parameter Spherical shaped nanoparticles result in highest entropy while the platelet shaped nanoparticles offer lowest entropy.The most optimal value of entropy is obtained to be zero when Re, volume fraction Skin friction of nanofluid with wall elevates with higher values of Reynolds number Re.Mass transfer decreases with increase in both volume fractions Heat transfer in the fluid is highest in case of platelet shaped nanoparticles and lowest in case of spherical shaped nanoparticles.This study can be further carried out in future by fractional modeling for various nanofluid models in both Buongiorno and two phase cases.The objective of current manuscript is modeling and computation of entropy generation and optimization in hybrid nanofluid with different nanoparticle shape factors. The base fluid in current study is blood while the two nanoparticles are radium


Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease by Yanan Xu et al., https://doi.org/10.1111/cns.14238.The cover image is based on the Review Article


The most common approach in transcriptomics (RNA-seq and microarrays) is differential gene expression analysis (DGEA). Differentially expressed genes (DEGs) may be responsible for phenotypic differences between various biological conditions. An alternative approach is gene coexpression analysis, which detects groups of genes with similar expression patterns across unrelated sets of transcriptomic data from the same organism. Coexpressed genes tend to be involved in similar biological processes. This Special Issue includes 12 research articles and one review on the topic of differential gene expression and coexpression. This review is an introduction to the basic methods of coexpression analysis, while the research articles describe both software and tools that assist in the execution of differential gene expression and coexpression analysis, as well as computational workflows that reveal new biological knowledge.dcap-1 knockout and wild type roundworms, Borbolis et al. [dcap-1) in the silencing of spermatogenic genes during late oogenesis and in the suppression of aberrant immune gene rise during aging in Caenorhabditis elegans. Yoon et al. [Through a microarray-based comparison of n et al.  revealedn et al.  identifin et al.  used a bn et al.  identifin et al.  were abln et al.  showed tn et al.  assessedn et al.  offered n et al. , a web an et al.  is a Linn et al.  is a webn et al.  is an opΤhe guest editors are grateful to all authors for their contributions to this Special Issue. Their works enlighten various aspects of differential gene expression and coexpression analyses, starting from transcriptomics data production and automated data acquisition from public repositories, followed by comprehensive analysis and meta-analysis applications and downstream analysis tools. Some publications presented bioinformatics pipelines used for the discovery of cancer biomarkers. We are looking forward to the presentation of novel computational pipelines and biological discoveries in the Special Issue “Differential Gene Expression and Coexpression 2.0”.


Biomedical sensors are the key units of medical and healthcare systems. The development focus of this topic is to use new technology and advanced functional biocompatible materials to design miniature, intelligent, reliable, multifunctional, low-cost, and efficient sensors. The last two decades have seen unprecedented growth in the employment of advanced sensors, which enable the detection of critical biomarkers for the early diagnosis of human diseases and the monitoring of human physiological signals for assessments in healthcare and biomedical applications. This rapid progress in both sensor technology development and its applications is mainly due to the quickly advancing development of micro/nanofabrication, manufacturing techniques, and advanced materials, as well as the increasing demand for the development of fast, simple, and sensitive measurement techniques that are capable of accurately and reliably monitoring biological samples in real time. The development of biomedical sensors is driven by the requirements of the medical field. The screening and continuous monitoring of patients with sensors has become increasingly important. A huge growth in the demand for home care will certainly promote the development of disposable sensors or telemedicine. This also puts forward requirements for future medical sensors.This Special Issue aims to provide an overview of recent advancements in the area of sensing technologies, including of sensors and platforms with a focus on functional materials, novel sensing mechanisms, design principles, fabrication and characterization techniques, performance optimization methods, multifunctional and multiplex sensing platforms, and system integration strategies, which play crucial roles in many applications.Gökhan Güney et al.  used MedAthanasios Tsanas et al.  proposedNegin Foroughimehr et al.  demonstrDavid Burns et al.  presente2 = 0.48 and a standard deviation STD = 0.10, with a total system average delay of 192 ms. Compared with the previous study, this newly proposed system presented a higher accuracy and was more suitable for real-time leg muscle activity estimation during walking.In the study by Zixi Gu et al. , a real-Chisaki Miura et al.  aimed toRobert Karpiński et al.  proposedAarón Cuevas-López et al.  presenteSheng-Wei Pan et al.  proposedLalita Chopra et al.  preparedWenfeng Zheng et al.  proposedRobert Karpiński et al.  aimed toDan Wang et al.  exploredPablo Campo-Prieto et al.  exploredWe would like to express our profound appreciation to the authors and reviewers who made this Special Issue possible. In the time it took to complete this Special Issue, our reviewers and authors contributed tremendous efforts to improve the paper’s quality and thus guarantee the high standard of this Special Issue.