bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of drug-naive children with attention-deficit/hyperactivity disorder from typical development controls using resting-state fMRI and graph theoretical approach
Authors: Rezaei Masoud , Zare Hoda , Hakimdavoodi Hamidreza , Nasseri Shahrokh , Hebrani Paria
Published: August 2022

Background and objectives

The study of brain functional connectivity alterations in children with Attention-Deficit/Hyperactivity Disorder (ADHD) has been the subject of considerable investigation, but the biological mechanisms underlying these changes remain poorly understood. Here, we aim to investigate the brain alterations in patients with ADHD and Typical Development (TD) children and accurately classify ADHD children from TD controls using the graph-theoretical measures obtained from resting-state fMRI (rs-fMRI).

Materials and methods

We investigated the performances of rs-fMRI data for classifying drug-naive children with ADHD from TD controls. Fifty six drug-naive ADHD children (average age 11.86 ± 2.21 years; 49 male) and 56 age matched TD controls (average age 11.51 ± 1.77 years, 44 male) were included in this study. The graph measures extracted from rs-fMRI functional connectivity were used as features. Extracted network-based features were fed to the RFE feature selection algorithm to select the most discriminating subset of features. We trained and tested Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting (GB) using Peking center data from ADHD-200 database to classify ADHD and TD children using discriminative features. In addition to the machine learning approach, the statistical analysis was conducted on graph measures to discover the differences in the brain network of patients with ADHD.

Results

An accuracy of 78.2% was achieved for classifying drug-naive children with ADHD from TD controls employing the optimal features and the GB classifier. We also performed a hub node analysis and found that the number of hubs in TD controls and ADHD children were 8 and 5, respectively, indicating that children with ADHD have disturbance of critical communication regions in their brain network. The findings of this study provide insight into the neurophysiological mechanisms underlying ADHD.

Conclusion

Pattern recognition and graph measures of the brain networks, based on the rs-fMRI data, can efficiently assist in the classification of ADHD children from TD controls.
Objective speech intelligibility prediction using a deep learning model with continuous speech-evoked cortical auditory responses
Authors: Na Youngmin , Joo Hyosung , Trang Le Thi , Quan Luong Do Anh , Woo Jihwan
Published: August 2022

Auditory prostheses provide an opportunity for rehabilitation of hearing-impaired patients. Speech intelligibility can be used to estimate the extent to which the auditory prosthesis improves the user’s speech comprehension. Although behavior-based speech intelligibility is the gold standard, precise evaluation is limited due to its subjectiveness. Here, we used a convolutional neural network to predict speech intelligibility from electroencephalography (EEG). Sixty-four–channel EEGs were recorded from 87 adult participants with normal hearing. Sentences spectrally degraded by a 2-, 3-, 4-, 5-, and 8-channel vocoder were used to set relatively low speech intelligibility conditions. A Korean sentence recognition test was used. The speech intelligibility scores were divided into 41 discrete levels ranging from 0 to 100%, with a step of 2.5%. Three scores, namely 30.0, 37.5, and 40.0%, were not collected. The speech features, i.e., the speech temporal envelope (ENV) and phoneme (PH) onset, were used to extract continuous-speech EEGs for speech intelligibility prediction. The deep learning model was trained by a dataset of event-related potentials (ERP), correlation coefficients between the ERPs and ENVs, between the ERPs and PH onset, or between ERPs and the product of the multiplication of PH and ENV (PHENV). The speech intelligibility prediction accuracies were 97.33% (ERP), 99.42% (ENV), 99.55% (PH), and 99.91% (PHENV). The models were interpreted using the occlusion sensitivity approach. While the ENV models’ informative electrodes were located in the occipital area, the informative electrodes of the phoneme models, i.e., PH and PHENV, were based on the occlusion sensitivity map located in the language processing area. Of the models tested, the PHENV model obtained the best speech intelligibility prediction accuracy. This model may promote clinical prediction of speech intelligibility with a comfort speech intelligibility test.
Musical abilities in children with developmental cerebellar anomalies
Authors: Guinamard Antoine , Clément Sylvain , Goemaere Sophie , Mary Alice , Riquet Audrey , Dellacherie Delphine
Published: August 2022

Developmental Cerebellar Anomalies (DCA) are rare diseases (e.g., Joubert syndrome) that affect various motor and non-motor functions during childhood. The present study examined whether music perception and production are affected in children with DCA. Sixteen children with DCA and 37 healthy matched control children were tested with the Montreal Battery for Evaluation of Musical Abilities (MBEMA) to assess musical perception. Musical production was assessed using two singing tasks: a pitch-matching task and a melodic reproduction task. Mixed model analyses showed that children with DCA were impaired on the MBEMA rhythm perception subtest, whereas there was no difference between the two groups on the melodic perception subtest. Children with DCA were also impaired in the melodic reproduction task. In both groups, singing performance was positively correlated with rhythmic and melodic perception scores, and a strong correlation was found between singing ability and oro-bucco-facial praxis in children with DCA. Overall, children with DCA showed impairments in both music perception and production, although heterogeneity in cerebellar patient’s profiles was highlighted by individual analyses. These results confirm the role of the cerebellum in rhythm processing as well as in the vocal sensorimotor loop in a developmental perspective. Rhythmic deficits in cerebellar patients are discussed in light of recent work on predictive timing networks including the cerebellum. Our results open innovative remediation perspectives aiming at improving perceptual and/or production musical abilities while considering the heterogeneity of patients’ clinical profiles to design music-based therapies.
Case Report: Prolonged clinical benefit with sequential trastuzumab-containing treatments in a patient with advanced extramammary Paget disease of the groin
Authors: Zattarin Emma , Nichetti Federico , Ligorio Francesca , Mazzeo Laura , Lobefaro Riccardo , Fucà Giovanni , Peverelli Giorgia , Vingiani Andrea , Bianchi Giulia V. , Capri Giuseppe , de Braud Filippo , Vernieri Claudio
Published: August 2022

Extramammary Paget disease (EMPD) is a rare form of cutaneous, intraepithelial adenocarcinoma, which typically presents itself as an erythematous plaque originating from apocrine-gland rich regions, such as the vulva, the perianal region, the scrotum, the penis, or the axilla. EMPD patients typically have a good prognosis, with expected 5-year survival of 60%–92%, but it is estimated that about one-third of EMPD patients will develop lymph node or distant metastases. Treatment approaches for EMPD include locoregional therapies such as broad surgical resection, radiotherapy, or topical imiquimod, when the disease is localized, and chemotherapy and biological agents for advanced EMPD. We report the case of a 58-year-old man diagnosed with locally advanced, symptomatic HER2-overexpressing, AR-positive EMPD, who achieved long-term tumor control with a sequence of several trastuzumab-based treatments (more than 30 months with second-line carboplatin plus paclitaxel plus trastuzumab followed by trastuzumab maintenance; 9 months for third-line vinorelbine plus trastuzumab). Even if it is reported that AR expression occurs concomitantly with HER2 overexpression in more than half of the cases of EMPD, to the best of our knowledge, this is the first case report describing androgen receptor blockade therapy in combination with an anti-HER2 agent. Our patient did not benefit from androgen receptor blockade in combination with trastuzumab, thus suggesting that AR expression may simply reflect an intrinsic characteristic of the EMPD cell of origin, rather than tumor dependence upon AR signaling. Given the reported sensibility to anti-HER2 therapy, also new antibody drug conjugates targeting HER2 are worth exploring in the management of advanced EMPD.
Evaluation of aliphatic acid metabolism in bladder cancer with the goal of guiding therapeutic treatment
Authors: Song Tianbao , He Kaixiang , Ning Jinzhuo , Li Wei , Xu Tao , Yu Weimin , Rao Ting , Cheng Fan
Published: August 2022

Urothelial bladder cancer (BLCA) is a common internal malignancy with a poor prognosis. The re-programming of lipid metabolism is necessary for cancer cell growth, proliferation, angiogenesis and invasion. However, the role of aliphatic acid metabolism genes in bladder cancer patients has not been explored. The samples’ gene expression and clinicopathological data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Univariate, multivariate, and LASSO Cox regression were used to develop a BLCA prognostic model. GSVA was used to assess function, whereas pRRophetic was used to assess chemotherapeutic drug sensitivity. The twelve-gene signature may define the tumor immune milieu, according to the risk score model. We compared the expression of aliphatic acid metabolism genes in malignant and non-cancerous tissues and chose 90 with a false discovery rate of 0.05 for The Cancer Genome Atlas cohort. The prognostic risk score model can effectively predict BLCA OS. A nomogram including age, clinical T stage, gender, grade, pathological stage, and clinical M stage was developed as an independent BLCA prognostic predictor. The halfmaximal inhibitory concentration (IC50) was used to assess chemotherapeutic medication response. Sorafenib and Pyrimethamine were used to treat patients with low risk scores more sensitively than patients with high risk scores. Immunotherapy candidates with CMS1 exhibited higher risk ratings. The aliphatic acid prognostic risk score model can assess metabolic trends. Clinical stage and molecular subtype may be used to categorize individuals using the risk score.With this new paradigm, future cancer treatment and immunotherapy may be tailored to the patient’s exact requirements.
Mechanical and metabolic interplay in the brain metastatic microenvironment
Authors: Onwudiwe Killian , Burchett Alice A. , Datta Meenal
Published: August 2022

In this Perspective, we provide our insights and opinions about the contribution—and potential co-regulation—of mechanics and metabolism in incurable breast cancer brain metastasis. Altered metabolic activity can affect cancer metastasis as high glucose supply and demand in the brain microenvironment favors aerobic glycolysis. Similarly, the altered mechanical properties of disseminating cancer cells facilitate migration to and metastatic seeding of the brain, where local metabolites support their progression. Cancer cells in the brain and the brain tumor microenvironment often possess opposing mechanical and metabolic properties compared to extracranial cancer cells and their microenvironment, which inhibit the ease of extravasation and metastasis of these cells outside the central nervous system. We posit that the brain provides a metabolic microenvironment that mechanically reinforces the cellular structure of cancer cells and supports their metastatic growth while restricting their spread from the brain to external organs.
Comparative review of pharmacological therapies in individuals with HER2-positive advanced breast cancer with focus on hormone receptor subgroups
Authors: Umemneku-Chikere Chinyereugo M. , Ayodele Olubukola , Soares Marta , Khan Sam , Abrams Keith , Owen Rhiannon , Bujkiewicz Sylwia
Published: August 2022

Breast cancer is the fifth leading cause of cancer-related deaths worldwide. The randomized controlled trials (RCTs) of targeted therapies in human epidermal receptor 2 (HER2)–positive advanced breast cancer (ABC) have provided an evidence base for regulatory and reimbursement agencies to appraise the use of cancer therapies in clinical practice. However, a subset of these patients harbor additional biomarkers, for example, a positive hormone receptor status that may be more amenable to therapy and improve overall survival (OS). This review seeks to explore the reporting of evidence for treatment effects by the hormone receptor status using the RCT evidence of targeted therapies for HER2-positive ABC patients. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed to identify published RCTs. Extracted data were synthesized using network meta-analysis to obtain the relative effects of HER2-positive-targeted therapies. We identified a gap in the reporting of the effectiveness of therapies by the hormone receptor status as only 15 out of 42 identified RCTs reported hormone receptor subgroup analyses; the majority of which reported progression-free survival but not OS or the overall response rate. In conclusion, we recommend that future trials in ABC should report the effect of cancer therapies in hormone receptor subgroups for all outcomes.
What predicts the clinical benefits of PARP inhibitors in platinum-sensitive recurrent ovarian cancer: A real-world single-center retrospective cohort study from China
Authors: Zhang Depu , Li Shuo , Zhang Xinxin , Peng Jingwei , Zhang Shiqian
Published: August 2022

Objective

This study assessed the real-world application, effectiveness, and safety of olaparib and niraparib as maintenance therapies in patients with platinum-sensitive recurrent ovarian cancer (PSROC) in China and investigated clinical factors associated with prolonged benefits of poly ADP-ribose polymerase (PARP) inhibitors to help guide clinician treatment-decision making in daily practice.

Methods

This real-world single-center retrospective cohort study was conducted at the Shandong Cancer Hospital and Institute. Archival data of consecutive patients diagnosed with PSROC who achieved a complete response (CR) or partial response (PR) after the last platinum-based chemotherapy and treated with olaparib or niraparib as maintenance therapy from August 2018 to September 2021 were collected.

Results

Overall, 106 women were included in the cohort. Seventy-two (68%) patients were treated with olaparib, while 34 (32%) received niraparib; 99.1% of the patients were diagnosed with high-grade serous carcinoma, and 73.6% had FIGO stages III–IV. Approximately 71.7% of the patients had received PARP inhibitors after the second platinum-based line and 44.3% of the patients achieved a CR in their last platinum-based therapy. The median platinum-free interval (PFI) after the penultimate platinum-based therapy was 10 (95% CI: 10–13.6) months. The median PFS was 21 (95% CI: 13–24.5) months and the median CFI was 22 (95% CI: 16–26.5) months. Consistent with the univariate analysis, the multivariate analysis identified three independent factors associated with prolonged progression-free survival (PFS) and chemotherapy-free interval (CFI): breast cancer susceptibility gene (BRCA) mutant type (p = 0.005 and p = 0.003); PFI ≥12 months (p = 0.01 and p = 0.006); and CR to last platinum-based therapy (p = 0.016 and p = 0.019). It was found that there was no appreciable difference in any grade 3–4 hematological AE between patients who received olaparib and niraparib.

Conclusion

Maintenance treatment with olaparib and niraparib is effective and well tolerated for PSROC patients in real-world clinical practice. Three clinical factors were identified that predicted prolonged survival under maintenance therapy with PARP inhibitors: BRCA mutant type, PFI ≥12 months, and CR to last platinum-based therapy. These findings should be further confirmed with an appropriately powered analysis in studies with larger sample sizes.
Publication trends of research on conjunctival melanoma during 1997–2022: A 25-year bibliometric study
Authors: Xu Wei , Yang Ludi , Ge Shengfang , Jia Shichong , Gu Fen
Published: August 2022

Background

Conjunctival melanoma (CM) is a life-threatening ocular tumor with a high rate of local recurrence and metastasis. Our objective is to analyze research trends in CM field and compare contributions from different countries, institutions and authors.

Methods

We extracted all CM-related publications published from 1997 to 2022 from the Web of Science database and applied Microsoft Excel and VOSviewer to review publication data, analyze publication trends, and visualize relevant data.

Results

A total of 708 publications were identified. The United States contributed the most publications (280) and citations (8,781 times) with the highest H-index value (47). The Ophthalmic Plastic and Reconstructive Surgery, British Journal of Ophthalmology, American Journal of Ophthalmology and Cornea were the most productive journal concerning CM, and Shields CL, Shields JA, Jager MJ as well as Finger PT had published the most papers in the field. Keywords were classified into three clusters: clinical research, management-related research and genetic research. The keywords “primary acquired melanosis”, “metastasis” and “BRAF mutations” were most frequently emerged. According to the average appearing year (AAY), targeted therapy (AAY of 2019.0) and nivolumab (AAY of 2018.7) were identified as the main focuses of the field in the near future.

Conclusion

In the past 25 years, the United States, Germany, England and the Netherlands held the leading position in the CM research. A group of scholars made important contributions to CM research and will continue to guide cutting-edge research. Treatments that have been shown to be effective for advanced cutaneous melanoma, such as targeted therapy and immunotherapy, are potential focuses for future CM research.
Efficacy and safety of immune checkpoint inhibitors-combined antiangiogenic drugs in the treatment of hepatocellular carcinoma: A systematic review and meta analysis
Authors: Zhong Yu , Huo Hong , Dai Shuqi , Li Su
Published: August 2022

Background

Hepatocellular carcinoma is a pathological type of liver cancer and accounts for the majority of primary liver cancers. We conducted a meta-analysis to evaluate the efficacy and safety of immune checkpoint inhibitors in combination with antiangiogenic drugs in the treatment of hepatocellular carcinoma.

Methods

We searched scientific literature databases and clinical trials databases through May 2022 for required studies. Progression-free survival was taken as the main outcome, and overall survival, response rate and adverse events as secondary outcomes. These data were extracted, combined and used for meta-analysis to compare the treatment effect and safety of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced/unresectable/metastatic hepatocellular carcinoma.

Results

This study included 3 randomized controlled trials and 6 single-arm trials of immune checkpoint inhibitors in combination with antiangiogenic drugs in hepatocellular carcinoma. Meta-analysis showed that compared with single use, combination of the two can significantly improve PFS (HR=5.93, 95% CI=5.41, 6.45) and OS (HR=15.84, 95% CI=15.39, 16.28). The ORR and DOR of patients with combination therapy were HR=19.11, 95% CI=15.99, 22.22 and HR=12.26, 95% CI=10.32, 14.21, respectively. Common adverse reactions to combination therapy included hypertension (26.8%), diarrhea (23.6%), fatigue (23.8%), decreased appetite (22.8%), hypothyroidism (9.9%), and rash (14.5%).

Conclusion

In the treatment of advanced/unresectable/metastatic hepatocellular carcinoma, immune checkpoint inhibitors combined with antiangiogenic drugs achieved better survival benefits than alone. In addition, the combination therapy has tolerable safety.
Current perspectives on recurrent HPV-mediated oropharyngeal cancer
Authors: Guo Theresa , Kang Stephen Y. , Cohen Ezra E. W.
Published: August 2022

In the recent years, the prevalence of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) has increased significantly. Currently, nearly 80-90% of all oropharynx tumors are HPV-positive. In addition, it is now recognized that HPV-positive tumor status is associated with good prognosis and improved response to chemoradiation. However, within this setting, there are still patients with HPV-positive OPSCC who will experience recurrence. With the increasing incidence of HPV-mediated OPSCC, recurrent HPV disease is also becoming more prevalent and there is an increasing need to understand the unique presentation and treatment of recurrent HPV-mediated disease. In this review, we will discuss epidemiology of recurrent HPV-positive OPSCC, role of surgical salvage, re-irradiation, and the role of upcoming novel treatments and immunotherapy. Historically, recurrent oropharyngeal disease has been associated with poor prognosis and high morbidity. However, recent advances have transformed the landscape for salvage treatment of HPV-mediated OPSCC. Liquid biomarkers offer potential for early detection of recurrence, robotic techniques may reduce morbidity of surgical salvage, improvements in re-irradiation approaches reduce toxicities, and novel immune based therapies on the horizon are offering promising results. These advances combined with the improved prognosis of HPV-positive disease offer to transform our approach to recurrent disease of the oropharynx.
The diagnostic value of a nomogram based on multimodal ultrasonography for thyroid-nodule differentiation: A multicenter study
Authors: Yi Dan , Fan Libin , Zhu Jianbo , Yao Jincao , Peng Chanjuan , Xu Dong
Published: August 2022

Objective

To establish and verify a nomogram based on multimodal ultrasonography (US) for the assessment of the malignancy risk of thyroid nodules and to explore its value in distinguishing benign from malignant thyroid nodules.

Methods

From September 2020 to December 2021, the data of 447 individuals with thyroid nodules were retrieved from the multicenter database of medical images of the National Health Commission’s Capacity Building and Continuing Education Center, which includes data from more than 20 hospitals. All patients underwent contrast-enhanced US (CEUS) and elastography before surgery or fine needle aspiration. The training set consisted of three hundred datasets from the multicenter database (excluding Zhejiang Cancer Hospital), and the external validation set consisted of 147 datasets from Zhejiang Cancer Hospital. As per the pathological results, the training set was separated into benign and malignant groups. The characteristics of the lesions in the two groups were analyzed and compared using conventional US, CEUS, and elastography score. Using multivariate logistic regression to screen independent predictive risk indicators, then a nomogram for risk assessment of malignant thyroid nodules was created. The diagnostic performance of the nomogram was assessed utilizing calibration curves and receiver operating characteristic (ROC) from the training and validation cohorts. The nomogram and The American College of Radiology Thyroid Imaging, Reporting and Data System were assessed clinically using decision curve analysis (DCA).

Results

Multivariate regression showed that irregular shape, elastography score (≥ 3), lack of ring enhancement, and unclear margin after enhancement were independent predictors of malignancy. During the training (area under the ROC [AUC]: 0.936; 95% confidence interval [CI]: 0.902–0.961) and validation (AUC: 0.902; 95% CI: 0.842–0.945) sets, the multimodal US nomogram with these four variables demonstrated good calibration and discrimination. The DCA results confirmed the good clinical applicability of the multimodal US nomogram for predicting thyroid cancer.

Conclusions

As a preoperative prediction tool, our multimodal US-based nomogram showed good ability to distinguish benign from malignant thyroid nodules.
Hypoxic stress and hypoxia-inducible factors in leukemias
Authors: Magliulo Daniela , Bernardi Rosa
Published: August 2022

To cope with hypoxic stress, ancient organisms have developed evolutionally conserved programs centered on hypoxia-inducible transcriptional factors (HIFs). HIFs and their regulatory proteins have evolved as rheostats to adapt cellular metabolism to atmospheric oxygen fluctuations, but the amplitude of their transcriptional programs has tremendously increased along evolution to include a wide spectrum of physiological and pathological processes. The bone marrow represents a notable example of an organ that is physiologically exposed to low oxygen levels and where basal activation of hypoxia signaling appears to be intrinsically wired within normal and neoplastic hematopoietic cells. HIF-mediated responses are mainly piloted by the oxygen-labile α subunits HIF1α and HIF2α, and current literature suggests that these genes have a functional specification that remains to be fully defined. Since their identification in the mid 90s, HIF factors have been extensively studied in solid tumors, while their implication in leukemia has lagged behind. In the last decades however, many laboratories have addressed the function of hypoxia signaling in leukemia and obtained somewhat contradictory results. Suppression of HIFs expression in different types of leukemia has unveiled common leukemia-promoting functions such as stimulation of bone marrow neoangiogenesis, maintenance of leukemia stem cells and chemoresistance. However, genetic studies are revealing that a definition of HIF factors as bona fide tumor promoters is overly simplistic, and, depending on the leukemia subtype, the specific oncogenic event, or the stage of leukemia development, activation of hypoxia-inducible genes may lead to opposite consequences. With this article we will provide an updated summary of the studies describing the regulation and function of HIF1α and HIF2α in blood malignancies, spanning from acute to chronic, lymphoid to myeloid leukemias. In discussing these data, we will attempt to provide plausible explanations to contradictory findings and point at what we believe are areas of weakness in which further investigations are urgently needed. Gaining additional knowledge into the role of hypoxia signaling in leukemia appears especially timely nowadays, as new inhibitors of HIF factors are entering the clinical arena for specific types of solid tumors but their utility for patients with leukemia is yet to be determined.
Characterization of coagulation-related gene signature to predict prognosis and tumor immune microenvironment in skin cutaneous melanoma
Authors: Song Binyu , Chi Hao , Peng Gaoge , Song Yajuan , Cui Zhiwei , Zhu Yuhan , Chen Guo , Wu Junzheng , Liu Wei , Dong Chen , Wang Yuanyong , Xu Ke , Yu Zhou , Song Baoqiang
Published: August 2022

Backgroud

Skin cutaneous melanoma (SKCM) is an extremely metastatic form of skin cancer. However, there are few valuable molecular biomarkers, and accurate diagnosis is still a challenge. Hypercoagulable state encourages the infiltration and development of tumor cells and is significantly associated with poor prognosis in cancer patients. However, the use of a coagulation-related gene (CRG) signature for prognosis in SKCM, on the other hand, has yet to be determined.

Method

We used data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases to identify differentially expressed CRGs, then designed a prognostic model by using the LASSO algorithm, univariate and multivariate Cox regression analysis, and constructed a nomogram which was evaluated by calibration curves. Moreover, the Gene Expression Omnibus (GEO), GSE54467 was used as an independent validation. The correlation between risk score and clinicopathological characteristics, tumor microenvironment (TME), and immunotherapy was further analyzed.

Results

To develop a prognostic model, seven CRGs in SKCM patients related to overall survival (OS) were selected: ANG, C1QA, CFB, DUSP6, KLKB1, MMP7, and RABIF. According to the Kaplan-Meier survival analysis, an increased OS was observed in the low-risk group than in the high-risk group (P<0.05). Immunotherapy was much more beneficial in the low-risk group, as per immune infiltration, functional enrichment, and immunotherapy analysis.

Conclusions

The prognosis of SKCM patients may now be predicted with the use of a CRG prognostic model, thus guiding the development of treatment plans for SKCM patients and promoting OS rates.
Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma
Authors: Li Shanshan , Liu Tingzhi , Liu Hailing , Zhai Xiaohui , Cao Taiyuan , Yu Hongen , Hong Wanjia , Lin Xiaoru , Li Ming , Huang Yan , Xiao Jian
Published: August 2022

Background

One of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration.

Methods

We retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data via whole exome sequencing.

Results

Genomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling via NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells.

Conclusions

In this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.
Case report: Gross persistent rectal prolapse. A case treated without mesh using deep retrorectal dissection/suturing
Authors: Miyano Go , Yamada Shunsuke , Murakami Hiroshi , Lane Geoffrey J. , Yamataka Atsuyuki
Published: August 2022

A previously well 15-year-old male presented with a history of gross rectal prolapse (GRP) involving full-thickness rectal prolapse of increasing severity and incidence over 6 months that occurred with every bowel motion, varying from 10 to 40 cm. He denied constipation and passed a soft motion once daily, adeptly reducing his prolapsed rectum after each motion. This case illustrates technical challenges and planning for surgical intervention for optimal treatment in keeping with an FDA alert issued April, 2019 banning surgical mesh for pelvic organ prolapse. Preoperative fluoroscopic defecography confirmed rectal prolapse beginning with eversion of the anal verge identified on inspection. For surgery, general anesthesia was induced, he was placed in a Trendelenburg position, and four ports were inserted. The peritoneum was incised and blunt dissection used to expose the levator ani complex (LAC) taking care to prevent lateral nerve injury and preserve regional vascularity. Seven polypropylene sutures were used to fix the seromuscular posterior wall of the rectum to the median raphe of the LAC, the presacral fascia, and the periosteum of the sacral promontory. Operative time was 170 min. Postoperative recovery and progress were unremarkable. Currently, 5 years postoperatively, defecation is regular without recurrence of prolapse. For prolapse involving protrusion of the upper rectum without eversion of the anal verge, rectal fixation to the sacral promontory without further dissection beyond the peritoneal reflection is adequate, but when extensive prolapse is associated with eversion of the anal verge, more extensive blunt dissection from the peritoneal reflection to the LAC with multiple rectopexy sutures is valid for reducing risks for recurrence and eliminating mesh-related complications.
Diagnostic value of ultrasound in children with transverse testicular ectopia
Authors: Zhou Wei , Li Shoulin , Wang Hao , Yin Jianchun , Liu Xiaodong , Jiang Junhai , Zhou Guanglun , Wen Jianguo
Published: August 2022

Objective

The study aimed to investigate the diagnostic value of ultrasound in children’s transverse testicular ectopia (TTE).

Materials and methods

We retrospectively studies all TTE cases diagnosed in our hospital from January 2017 to December 2021. All cases were evaluated by ultrasound examination and compared to physical examination and diagnostic laparoscopy results.

Results

This study included 14 TTE patients in total, with a median age was 1.08 years. In the 14 TTE, physical examination found 10 TTE cases, of which nine testes were located in the opposite scrotum, one testis was located in the opposite groin, and the other four testes were not observed by physical examination. All cases were diagnosed by preoperative ultrasound, and nine testes were located in the opposite scrotum, two testes were located in the opposite groin, and three testes were located next to the opposite iliac vessel in the abdominal cavity. Preoperative ultrasound showed the ectopic spermatic cord in six cases (6/14, 42.8%) and persistent Müllerian duct syndrome (PMDS) in one case (1/14, 7%). Diagnostic laparoscopy finally confirmed 14 cases of TTE, which was consistent with preoperative ultrasound, and the coincidence rate was 100% (14/14). Among the 14 cases of TTE, diagnostic laparoscopy showed that 12 cases had ectopic spermatic vessels and vas deferens (12/14, 85.7%), and six cases were associated with PMDS (6/14, 42.8%). When TTE was associated with the ectopic spermatic cord and PMDS, the diagnostic performance of diagnostic laparoscopy was better than that of preoperative ultrasound (P < 0.05). The testis volume of the affected side of TTE was less than that of the contralateral testis (P < 0.05).

Conclusion

Ultrasonography is very helpful for the preoperative diagnosis of TTE in children, and it is suitable as a non-surgical method for locating ectopictestis. Preoperative assessment of the exact presence of PMDS is difficult and unclear. This may be related to factors such as pelvic developmental stages in infancy, examination techniques, and atypical imaging findings of PMDS.
Modified thoracoscopic wedge resection of limited peripheral lesions in S10 for children with congenital pulmonary airway malformation: Initial single-center experience
Authors: Guo Rui , Zhai Yunpeng , Zhang Shisong , Zhao Huashan , Xu Hongxiu , Lv Longfei
Published: August 2022

Objective

The present study aimed to evaluate the safety and feasibility of modified thoracoscopic wedge resection of limited peripheral lesions in the posterior basal segment (S10) in children with congenital pulmonary airway malformation (CPAM).

Materials and methods

We retrospectively analyzed the clinical data of children with CPAM who underwent thoracoscopic modified wedge resection at our institution from November 2020 to February 2022. The surgical method was as follows: we marked the external boundary of the lesion with an electric hook, dissected and retained the segmental vein between the lesion and normal lung tissue as the internal boundary, cut the arteries, veins, and bronchus entering the lesion, and cut and sealed the lung tissue between the internal and external boundaries with LigaSure™ to complete the modified wedge resection.

Results

A total of 16 patients were included, aged 3.8−70.0 months and weighing 6.5−21.0 kg. The intraoperative course was uneventful in all patients. The median operation time and intraoperative bleeding volume were 74 min (50−110 min) and 5 mL (5−15 mL), respectively. The median postoperative drainage tube indwelling time was 3 days (2−4 days), and the median postoperative hospital stay was 6 days (4−8 days). Pathological diagnosis included two cases of type 1, 10 cases of type 2, and four cases of type 3 CPAM. There were no cases of intraoperative conversion, surgical mortality, or major complications. However, subcutaneous emphysema occurred in two children, which spontaneously resolved without pneumothorax orbronchopleural fistula development. All patients were followed up for a median period of 10 months (3–18 months), and there were no cases of hemoptysis or residual lesions on chest computed tomography.

Conclusion

Modified thoracoscopic wedge resection via the inferior pulmonary ligament approach is safe and feasible for children with CPAM with limited peripheral lesions in S10.
Colorimetric loop-mediated isothermal amplification assay for detection and ecological monitoring of Sarocladium oryzae, an important seed-borne pathogen of rice
Authors: Choudhary Prassan , Goswami Sanjay Kumar , Chakdar Hillol , Verma Shaloo , Thapa Shobit , Srivastava Alok Kumar , Saxena Anil Kumar
Published: August 2022

Accurate and timely disease detection plays a critical role in achieving sustainable crop protection. Globally, rice has been a staple crop for centuries plagued by the diseases that greatly hamper its productivity. Sheath rot, an emerging disease of rice caused by the seed-borne pathogen Sarocladium oryzae, has reportedly caused heavy losses to agricultural produce in recent years. Our study has led to the development and validation of a LAMP assay for early detection of S. oryzae, the causal agent of sheath rot from the live-infected tissues, seeds, weeds, and environmental samples. The assay could detect as low as 1.6 fg/μl of the pathogen in 15 min. The assay was implemented to bio-surveil the presence of this pathogen by testing it on three weed species (Echinochloa colona, Echinochloa crus-galli, and Cyperus teneriffae) growing around the rice fields. The results showed the presence of the pathogen in two of the weed species viz. E. colona and E. crus-galli. The assay was used to test 13 different rice varieties for the presence of S. oryzae in seeds. In total, three of the varieties did not show the presence of S. oryzae in their seeds while the rest were found to harbor the pathogen. The developed assay can effectively be used to detect and screen the presence of S. oryzae in live samples including seeds and field soil.
Genome-wide comparative analysis of the nucleotide-binding site-encoding genes in four Ipomoea species
Authors: Si Zengzhi , Wang Lianjun , Qiao Yake , Roychowdhury Rajib , Ji Zhixin , Zhang Kai , Han Jinling
Published: August 2022

The nucleotide-binding site (NBS)-encoding gene is a major type of resistance (R) gene, and its diverse evolutionary patterns were analyzed in different angiosperm lineages. Until now, no comparative studies have been done on the NBS encoding genes in Ipomoea species. In this study, various numbers of NBS-encoding genes were identified across the whole genome of sweet potato (Ipomoea batatas) (#889), Ipomoea trifida (#554), Ipomoea triloba (#571), and Ipomoea nil (#757). Gene analysis showed that the CN-type and N-type were more common than the other types of NBS-encoding genes. The phylogenetic analysis revealed that the NBS-encoding genes formed three monophyletic clades: CNL, TNL, and RNL, which were distinguished by amino acid motifs. The distribution of the NBS-encoding genes among the chromosomes was non-random and uneven; 83.13, 76.71, 90.37, and 86.39% of the genes occurred in clusters in sweet potato, I. trifida, I. triloba, and I. nil, respectively. The duplication pattern analysis reveals the presence of higher segmentally duplicated genes in sweet potatoes than tandemly duplicated ones. The opposite trend was found for the other three species. A total of 201 NBS-encoding orthologous genes were found to form synteny gene pairs between any two of the four Ipomea species, suggesting that each of the synteny gene pairs was derived from a common ancestor. The gene expression patterns were acquired by analyzing using the published datasets. To explore the candidate resistant genes in sweet potato, transcriptome analysis has been carried out using two resistant (JK20 and JK274) and susceptible cultivars (Tengfei and Santiandao) of sweet potato for stem nematodes and Ceratocystis fimbriata pathogen, respectively. A total of 11 differentially expressed genes (DEGs) were found in Tengfei and JK20 for stem nematodes and 19 DEGs in Santiandao and JK274 for C. fimbriata. Moreover, six DEGs were further selected for quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis, and the results were consistent with the transcriptome analysis. The results may provide new insights into the evolution of NBS-encoding genes in the Ipomoea genome and contribute to the future molecular breeding of sweet potatoes.
Nucleo-cytoplasmic interactions affecting biological performance of Lipaphis erysimi in Brassica juncea
Authors: Singh Naveen , Dhillon Mukesh K.
Published: August 2022

Hybrids have been successfully used to improve crop productivity, including Brassicas. Nucleo-cytoplasmic interactions have been reported to influence the expression of resistance to insect pests in several crops. We studied the effects of Cytoplasmic Male Sterility (CMS) in Brassica juncea carrying alien cytoplasms and their respective maintainer (B) lines on the antibiosis mechanism of resistance, involving development, survival, reproduction potential and population build-up of mustard aphid, Lipaphis erysimi, and the levels of defense phyto-chemicals. Present findings revealed that the numbers of aphids/plant, aphid multiplication rate and aphid resistance index were lower on ber CMS under natural, mori CMS under artificial infestation conditions, and juncea under both the test conditions indicating nucleo-cytoplasmic interactions for aphid reaction. Across cytoplasms, nymphal, reproductive and total developmental periods were significantly longer on SEJ 8, NPJ 161, LES 39, and NPJ 93, while the reproductive potential and survival were lower on PM 30, Pusa Tarak and SEJ 8 as compared to other nuclear backgrounds. Across nuclear backgrounds, nymphal, reproductive and total developmental periods were significantly longer on ber CMS, while reproductive potential and survival were lower on ber and mori CMS as compared to other cytoplasms. Total glucosinolates were significantly greater and myrosinase lower in Pusa Agrani, SEJ 8, LES 39, PM 30, NPJ 112, and Pusa Tarak as compared to the other nuclear backgrounds. Furthermore, total glucosinolates were significantly greater and myrosinase lower in ber CMS and juncea as compared to other cytoplasms. The studies suggest that CMS as well as cytoplasmic and nuclear gene interactions regulate the expression of defense compounds such as glucosinolates and determine the expression of resistance/susceptibility to L. erysimi. These findings shall help in identification of suitable L. erysimi tolerant nucleo-cytoplasmic combinations for their deployment in B. juncea hybrid breeding program.
Functional characterization of a catalytically promiscuous tryptophan decarboxylase from camptothecin-producing Camptotheca acuminata
Authors: Qiao Chong , Chen Fei , Liu Zhan , Huang Tianfang , Li Wei , Zhang Guolin , Luo Yinggang
Published: August 2022

Tryptophan decarboxylases (TDCs) are a group of pyridoxal 5′-phosphate-dependent enzymes involved in the enzymatic conversion of tryptophan into tryptamine, a critical biogenic amine. We herein mined and cloned a TDC-encoding gene, CaTDC3, from camptothecin-producing plant Camptotheca acuminata. The intact CaTDC3 was heterologously overexpressed in Escherichia coli and the recombinant CaTDC3 was purified to homogeneity. High-performance liquid chromatography (HPLC)-diode array detector (DAD) and high resolution mass spectrometry (HRMS) data analyses of the CaTDC3-catalyzed reaction mixture confirmed the catalytically decarboxylative activity of CaTDC3. CaTDC3 shows strict stereoselectivity for L-tryptophan. Homology modeling and molecular docking implied CaTDC3’s recognition of L-tryptophan derivatives and analogs. Substrate scope investigations revealed that the appropriate substituent groups on the indole ring, i.e., hydroxylated and halogenated L-tryptophans, could be recognized by CaTDC3 and the decarboxylation reactions generated the corresponding tryptamines. The Cβ -methyl-L-tryptophans were decarboxylated by CaTDC3 efficiently. 1-Thio-L-tryptophan, the NH group of the indole ring replaced by an S atom, could be decarboxylated by CaTDC3. CaTDC3 catalyzed the decarboxylation of 7-aza-L-tryptophan, an N displacement of the C on the aromatic ring, to afford 7-aza-tryptamine. L-Kynurenine, an L-tryptophan degradation product, could be decarboxylated by CaTDC3. The present works uncover a catalytically promiscuous TDC and the TDC is a versatile decarboxylase in synthetic biology for specialized pharmaceutically important substances.
Impact of Inclusive Leadership on Innovation Performance During Coronavirus Disease 2019 Outbreak: Mediating Role of Employee Innovation Behavior and Moderating Role of Psychological Empowerment
Authors: Gupta Shuchi , Nawaz Nishad , Tripathi Abhishek , Arif Chaudhry Shafaq , Agrawal Khushbu
Published: August 2022

This study investigates the effect of inclusive leadership on innovation performance with a mediating role of employee innovation behavior and the moderating role of psychological empowerment (PE). Supervisors and employees of Saudi manufacturing firms are the participants of this study. This study used a quantitative research technique with a cross-sectional approach and a self-administrative survey questionnaire to collect the data. The data were analyzed by using the Smart PLS 3 software. The results depict that inclusive leadership has a significant positive impact on the firm’s innovation performance. Employees’ innovation behavior has a significant mediating effect on the association of inclusive leadership and innovation performance. Findings revealed that PE has an important moderating role in the association of inclusive leadership and innovation performance. The findings of this study contribute to the body of knowledge by finding that inclusive leadership has a significant effect on the firm’s innovative performance and PE is crucial to enhance innovation performance.