Case Of LS Research Articles

6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation

Abstract Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None. Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(<1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was <0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A>G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS. Presentation: 6/1/2024

Key factors governing the direction of SH0 mode guided waves generated by FeCo strip-based magnetostrictive sensor

Magnetostrictive sensors (MsS) are widely used to generate ultrasonic guided waves of SH0 mode for the purpose of detecting defects in plate-like structures. An MsS commonly employs a rectangular magnetostrictive strip and a sensor unit (including detection coil and magnet) to generate SH0 waves. However, the effect of coverage range of static magnetic field (Ls) and dynamic magnetic field (LD) on the SH0 wave generation direction has not been fully explored. So far, the cases of LS<<LD and LD>>LS are seldom discussed in the development of MsS for generating SH0 mode. In this study, the key factor governing the direction of SH0 mode generated by FeCo strip-based MsS was experimentally clarified. The transition phenomenon in the generation direction of SH0 wave was observed while the combination parameters crossing the control line of Ls≈LD. The phenomenon could be interpreted by the alterations in the operation mechanism of Wiedemann effect and reversed Wiedemann effect. As a result, the generation direction of SH0 mode could be tuned along the static magnetic field (Ls<<LD), the dynamic magnetic field (Ls>>LD) or the direction of both static and dynamic magnetic fields (Ls≈LD). The findings in this study is of benefit for guiding the design of MsS array with the tunable generation direction of SH0 mode.

Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation.

Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%). More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.

Sliding methods for dual fractional nonlinear divergence type parabolic equations and the Gibbons’ conjecture

Abstract In this paper, we consider the general dual fractional parabolic problem ∂ t α u ( x , t ) + L u ( x , t ) = f ( t , u ( x , t ) ) in R n × R . ${\partial }_{t}^{\alpha }u\left(x,t\right)+\mathcal{L}u\left(x,t\right)=f\left(t,u\left(x,t\right)\right) \text{in} {\mathbb{R}}^{n}{\times}\mathbb{R}.$ We show that the bounded entire solution u satisfying certain one-direction asymptotic assumptions must be monotone increasing and one-dimensional symmetric along that direction under an appropriate decreasing condition on f. Our result here actually solves a well-known problem known as Gibbons’ conjecture in the setting of the dual fractional parabolic equations. To overcome the difficulties caused by the nonlocal divergence type operator L $\mathcal{L}$ and the Marchaud time derivative ∂ t α ${\partial }_{t}^{\alpha }$ , we introduce several new ideas. First, we derive a general weighted average inequality corresponding to the nonlocal operator L $\mathcal{L}$ , which plays a fundamental bridging role in proving maximum principles in unbounded domains. Then we combine these two essential ingredients to carry out the sliding method to establish the Gibbons’ conjecture. It is worth noting that our results are novel even for a special case of L $\mathcal{L}$ , the fractional Laplacian (−Δ) s , and the approach developed in this paper will be adapted to a broad range of nonlocal parabolic equations involving more general Marchaud time derivatives and more general non-local elliptic operators.

BH03 Lipoedematous scalp occurring in two female siblings: further evidence of a genetic role?

Abstract Lipoedematous scalp (LS) is a rare disorder characterized by thickening of the adipose subcutaneous scalp layer. We describe an unusual case of two female siblings presenting with the same condition. A 58-year-old black Caribbean woman presented with a 7-year history of an itchy, painful and scaly scalp, without any associated hair loss. Mycology had been negative. There was a history of paranoid schizophrenia and bipolar disorder, for which she was taking olanzapine. Body mass index (BMI) was 39 mg kg–2. Examination revealed a thickened scalp with a spongy consistency, with no associated surface change or hair loss. Scalp ultrasound was performed, demonstrating a scalp thickness of 12 mm at the vertex (normal range 5–6 mm). Scalp biopsy revealed prominent fat in the dermis around the hair follicles, with follicular distortion and some focal perifollicular fibrosis. Based on these findings, a clinicopathological diagnosis of LS was made. The patient’s 63-year-old sister presented with similar scalp symptoms. She had a background of diabetes mellitus type 2, migraine and hypomania and was taking metformin, gliclazide, atorvastatin, sodium valproate and mirabegron; her BMI was 26 mg kg–2. Scalp ultrasound revealed diffuse thickening of the subcutaneous fat measuring 9 mm at the vertex, which was also consistent with a diagnosis of LS. The pathogenesis of LS is poorly understood. It is more common in females, and there appears to be an association between LS and obesity (Yasar S, Gunes P, Serdar ZA, Tosun I. Clinical and pathological features of 31 cases of lipedematous scalp and lipedematous alopecia. Eur J Dermatol 2011; 21:520–8). Studies have implicated leptin, a hormone that regulates distribution of adipose tissue. There is limited evidence for a genetic role in LS. We identified three female cases of LS in the literature with a positive family history in their daughters (Yasar et al.) but no cases of siblings with LS. We identified one reported case of the related disorder, lipoedematous alopecia, occurring in a pair of female siblings (Koç Yıldırım S, İğde B. Lipedematous alopecia: report of two female siblings. J Cosmet Dermatol 2022; 21:1324–5). Our case highlights a possible genetic role in the pathogenesis of LS, and further studies are needed to investigate this link further.

Correlation between 5-HTTLPR gene polymorphism and cognitive function of traumatic stress in Chinese Han children.

BackgroundPost-traumatic stress disorder (PTSD) is a trauma-related psychological disorder with serious social and familial impacts. The involvement of 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) in numerous mental disorders has been documented. This study explored the correlation between 5-HTTLPR gene polymorphism and cognitive function in Chinese Han children with PTSD.MethodsA total of 60 PTSD children treated from December 2019 to December 2021 were selected as study participants, with another 60 healthy children selected as controls. We assessed the cognitive function of participants using the Mini-Mental State Examination (MMSE). Additionally, the PTSD level was estimated by the Children’s Revised Impact of Event Scale (CRIES). The 5-HTTLPR gene polymorphism was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The genotype and allele frequency were evaluated via case-control association analysis.ResultsChildren in the PTSD group showed low MMSE scores and high CRIES scores. In terms of genotype, cases of LL, LS, and SS in PTSD children were 4 (6.67%), 20 (33.3%), and 36 (60.00%), and 18 (30.00%), 28 (46.67%), and 14 (23.33%) cases in healthy controls. In terms of allele gene frequency, incidences of L and S were 23.33% and 76.67% in PTSD children, respectively, and were 53.33% and 46.67% in healthy controls, respectively. Moreover, the CRIES and MMSE scores of LS and SS genotypes were evidently different from those of LL genotype in PTSD children.ConclusionsPolymorphism of the 5-HTTLPR gene is correlated with cognitive dysfunction in Chinese Han children with PTSD.

Lynch Syndrome-Associated Endometrial Cancer With Combined EPCAM-MSH2 Deletion: A Case Report.

BackgroundLynch syndrome (LS), an autosomal dominant disorder, is characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes like MSH2. EPCAM deletions cause a minority (3%) of LS cases. However, there are only a few reports of LS-associated endometrial cancer (LS-EC) induced by the inactivation of the MSH2 gene due to EPCAM deletions.Case PresentationWe present the case of a 45-years old woman diagnosed with endometrial cancer (EC). Definitive surgery revealed meso-differentiated endometrioid adenocarcinoma, stage IA without lymph-vascular space invasion. Four months later, she received radiation therapy (125I radioactive seeds implantation), and platinum-containing regimen combined chemotherapy because of vaginal stump metastasis of EC. After five years, we performed immunohistochemistry (IHC) on pelvic mass because of presacral metastatic lymph node. IHC showed the absence of MSH2 and MSH6 protein expression in the pelvic mass tissue. Peripheral blood was used for genetic testing based on her cancer diagnosis and family history of cancer in close relatives. Genetic testing revealed deletions of exon 8 and 9 in EPCAM and deletions of exon 1 and 8 in MSH2; thus, we diagnosed the presence of LS. The patient underwent interstitial brachytherapy (BT) of the presacral metastatic lymph node.ConclusionThis case highlights that patients with LS-EC who are carriers of combined EPCAM-MSH2 deletion might experience better oncologic outcomes even with early recurrence.

P53/CK17 Dual Stain Improves Accuracy of Distinction Between Differentiated Vulvar Intraepithelial Neoplasia and Its Mimics.

Accurate diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) is challenging, in part due to the sometimes subtle nature of its atypia. Many dVIN lesions demonstrate aberrant p53 staining; however, staining patterns overlap between dVIN and benign/reactive entities. We evaluate a p53/CK17 dual stain in an initial cohort of dVIN (n=30), benign vulvar skin (n=5), lichen sclerosus (LS, n=10), lichen simplex chronicus (LSC, n=10), and pseudoepitheliomatous hyperplasia (PEH, n=10). In the initial cohort, aberrant p53 staining was seen only in dVIN (50%, 15/30). Equivocal p53 staining patterns were seen in dVIN (37%, 11/30), LS (50%, 5/10), LSC (40%, 4/10), and PEH (40%, 4/10). All 30 dVIN cases were positive for CK17 (strong partial-thickness or full-thickness staining), but positive CK17 staining was also seen in LS (70%, 7/10), LSC (50%, 5/10), and PEH (100%, 10/10). In the initial cohort, the combination of aberrant p53 and positive CK17 was seen only for dVIN (50%, 15/30). Forty cases of LS with known follow-up (20 with progression to dVIN, 20 without) were stained to assess prognostic value. Three LS cases showed aberrant p53 staining with CK17 positivity; all progressed to dVIN. Equivocal p53 staining and CK17 positivity were seen in cases with and without progression. The p53/CK17 dual stain is more diagnostically useful than either stain alone. Negative/focal staining for CK17 argues against a diagnosis of dVIN, while aberrant p53 staining with CK17 positivity strongly supports the diagnosis.

EP.FRI.147 Abdominal Variant Lemierre’s Syndrome: A Case Study and literature review

Abstract Background Lemierre’s Syndrome (LS) is a rare condition with a prevalence of around 0.6-2.3 cases per million of population. Typically, LS starts with a Fusobacterium Necophorum oropharyngeal infection which spreads rapidly causing infective thrombophlebitis, classically of the internal jugular. This is a life-threatening condition which left untreated has a mortality of 90%. In less than 10% of LS cases thrombophlebitis occurs outside of the internal jugular vein. These atypical presentations can result in delay in diagnosis thus treatment and hence have an increased risk of mortality. Case Report Here we present a case report of a patient with Abdominal Variant Lemierre’s syndrome. A 47-year-old female with no past medical history was admitted to the emergency department with severe epigastric abdominal pain. The patient was stable, her National Early Warning Score (NEWS) was 2, blood tests on admission showed thrombocytopenia (Hb 121g/dl, Platelets 50x109/l, WCC 17.1x1012/l), raised CRP 299mg/l and deranged Liver Function Tests (Total protein 56g/l, Bilirubin 45mg/dl, ALT 94U/L, AlkPhos- 121U/L). A Venous Blood Gas was abnormal with Lactate 2.1mmol/l. A sepsis pathway was initiated. The blood cultures grew Fusobacterium Necophorum. MRI Imaging confirmed the diagnosis of Abdominal Variant Lemierre’s Syndrome. Haematology and Microbiology were consulted. The patient was treated with antibiotics and anticoagulation and was discharged 29 days later, she has made a full recovery. Conclusion This case highlights the importance of sepsis vigilance in Acute General Surgery admissions and emphasises that multidisciplinary teamwork is essential to achieve effective and prompt treatment for patients.

Inadequate Engagement in HIV Care Among People With HIV Newly Diagnosed With a Sexually Transmitted Disease: A Multijurisdictional Analysis.

A key challenge of HIV surveillance-based HIV care reengagement is locating people living with HIV (PLWH) who seem to be out of care to reengage them in care. Providing reengagement services to PLWH diagnosed with a sexually transmitted disease (STD)-individuals who are in jurisdiction and connected to the health care system-could be an efficient means of promoting HIV treatment and reducing HIV transmission. Early and late syphilis (ES/LS) and gonorrhea (GC) cases diagnosed in 2016 and 2017 in Louisiana, Michigan, Mississippi, Oregon, Rhode Island, and Texas were matched to each state's HIV surveillance data to determine the proportion of PLWH with these infections who (1) did not have evidence of a CD4 count or viral load in the prior ≥13 months (out of care) or (2) had a viral load ≥1500 copies/mL on their most recent HIV RNA test before STD diagnosis (viremic). Previously diagnosed HIV infection was common among persons diagnosed with ES (n = 6942; 39%), LS (n = 4329; 27%), and GC (n = 9509; 6%). Among these ES, LS, and GC cases, 26% (n = 1543), 33% (n = 1113), and 29% (n = 2391) were out of HIV medical care or viremic at the time of STD diagnosis. A large proportion of STD cases with prior HIV diagnosis are out of care or viremic. Integrating relinkage to care activities into STD partner services and/or the use of matching STD and HIV data systems to prioritize data to care activities could be an efficient means for relinking patients to care and promoting viral suppression.

Editorial Comment.

You have accessJournal of UrologyReview Article1 Oct 2021Editorial CommentThis article comments on the following:One-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-Analysisis a letter which has replyReply by Authors Benjamin Dropkin Benjamin DropkinBenjamin Dropkin Department of Urology,University of Kentucky,Lexington, Kentucky More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001870.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Minimally invasive treatment options for LS strictures include topical and intraurethral steroids and extended meatotomy. Urethroplasty is required if these treatments fail. Substitution urethroplasty using genital skin flaps performs poorly in the setting of LS and has been strongly discouraged (reference 33 in article). Two-stage repair utilizing BMG demonstrated reasonable long-term success rates and became the standard of care. The requisite second procedure, substantial revision rate, and potential for cosmetic and sexual ramifications are inconveniences that could potentially be avoided with a single-stage BMG technique, which has proven to be highly successful for non-LS strictures. Whether similar results can be achieved in the LS population remains a topic of debate among reconstructive urologists. The meta-analysis by Kurtzman et al offers the strongest available support for the use of single-stage BMG urethroplasty in the treatment of LS strictures. The authors analyzed 21 retrospective case series that included 625 LS patients treated with single-stage BMG urethroplasty and found a pooled stricture recurrence rate of 10%, which rose to 18% when the analysis was limited to studies with at least 24 months of followup. A subanalysis of the studies that reported outcomes from groups of men with LS and non-LS strictures found similar short-term recurrence rates and marginally poorer outcomes in LS cases with >24 months of followup. Of note, LS-strictures involving the penile urethra were significantly less likely to recur when approached via a perineal incision with penile invagination. Several limitations are notable. This study did not include an assessment of series reporting outcomes for 2-stage urethroplasty for LS strictures. Additionally, the authors appropriately advise caution in applying the results of this meta-analysis to patients with severe stricture disease, who lack a viable urethral plate and/or demonstrate a urethral lumen less than 5Fr. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of UrologyMay 25, 2021, 12:00:00 AMOne-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-AnalysisJournal of UrologyJul 23, 2021, 12:00:00 AMReply by Authors Volume 206Issue 4October 2021Page: 851-852 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin Dropkin Department of Urology,University of Kentucky,Lexington, Kentucky More articles by this author Expand All Advertisement Advertisement Loading ...

Co-occurrence of germline pathogenic variants for different hereditary cancer syndromes in patients with Lynch syndrome.

BackgroundLynch syndrome (LS) is a hereditary condition characterized by a high risk of colorectal cancer, endometrial cancer, and other neoplasia associated with germline alterations in DNA mismatch repair genes. The classical genetic diagnostic strategy for LS consists of the Sanger sequencing of genes associated with the suspected syndrome. Next‐generation sequencing (NGS) enables the simultaneous sequencing of a large number of hereditary cancer genes. Here, we aimed to study whether other germline pathogenic variants of hereditary cancer genes are present in patients with LS.MethodsA cohort of 84 probands with a previous genetic diagnosis of LS by Sanger sequencing was reanalyzed using NGS via a commercial panel of 94 hereditary cancer genes by hybrid capture. The American College of Medical Genetics and Genomics criteria were used to classify the clinical significance of the variants. The findings of NGS were confirmed by Sanger sequencing. When possible, genetic analyses of the new findings in the proband's relatives were also performed by Sanger sequencing.ResultsWe identified five families (6%), out of 84, with at least two germline pathogenic variants conferring to high or moderate risk in different dominant cancer‐predisposing genes: [MLH1‐BRCA2‐NBN], [MLH1‐BRCA1], [MSH2‐ATM], [MSH6‐NF1], and [MLH1‐FANCA]. Interestingly, only one out of these five families exhibited a clinical phenotype associated with the new pathogenic variants. The family with three pathogenic variants of the [MLH1‐BRCA2‐NBN] genes showed a high aggregation of tumors associated with LS and breast and ovarian cancer syndrome.ConclusionsOur results showed that the co‐occurrence of more than one pathogenic variant in cancer‐predisposing genes was remarkable among cases of LS. In most cases, no clinicial manifestations were associated with the secondary pathogenic variants. Further studies are needed to confirm these findings and elucidate their clinical impact. Reanalysis of LS families should be considered only in families with mixed clinical phenotypes.

Practice patterns and results of tumor and germline genetic evaluation of women with endometrial cancer in south Louisiana

The objectives were to describe rates of MMRd or MSI-H EC tumors, the prevalence of LS, the practice patterns of EC genetic evaluation and adherence to NCCN guidelines, and to identify disparities in the genetic evaluation of women with EC.A retrospective cohort study was performed on women with EC from 1/2013 to 12/2019, and information collected included demographics, personal and family history, EC diagnosis and treatment, and details of genetic evaluation. Statistical analysis included a multivariable logistic regression to adjust for all covariate effects simultaneously and Fisher exact tests of independence and Wilcoxon rank-sum tests to compare categorical and continuous covariates, respectively.Of the 286 women with EC, 80 EC tumors were tested, and 27.5% were MMRd or MSI-H. Of the 21 women who had germline testing, no cases of LS were identified. Before the NCCN recommended universal tumor testing, 17.6% of women had tumor testing performed compared to 60.0% after February of 2017 (OR = 2.51, 95% CI 1.89–3.32). Advanced cancer stage was nearly associated with an increased likelihood of tumor testing (OR = 1.40, 95% CI 1.00–1.97). No disparities were identified.We described patterns of genetic evaluation and tumor testing results for women with EC in south Louisiana and found similar rates of MMRd or MSI-H EC tumors as previously reported in other populations. Rates of tumor testing increased after the NCCN recommendation for universal tumor testing, but it is critical to identify weaknesses in this process and develop an algorithm to improve care for women with EC.

Drug Repositioning for Noonan and LEOPARD Syndromes by Integrating Transcriptomics With a Structure-Based Approach.

Noonan and LEOPARD syndromes (NS and LS) belong to a group of related disorders called RASopathies characterized by abnormalities of multiple organs and systems including hypertrophic cardiomyopathy and dysmorphic facial features. There are no approved drugs for these two rare diseases, but it is known that a missense mutation in PTPN11 genes is associated with approximately 50% and 70% of NS and LS cases, respectively. In this study, we implemented a hybrid computational drug repositioning framework by integrating transcriptomic and structure-based approaches to explore potential treatment options for NS and LS. Specifically, disease signatures were derived from the transcriptomic profiles of human induced pluripotent stem cells (iPSCs) from NS and LS patients and reverse correlated to drug transcriptomic signatures from CMap and L1000 projects on the basis that if disease and drug transcriptomic signatures are reversely correlated, the drug has the potential to treat that disease. The compounds that were ranked top based on their transcriptomic profiles were docked to mutated and wild-type 3D structures of PTPN11 by an adjusted Induced Fit Docking (IFD) protocol. In addition, we prioritized repositioned candidates for NS and LS by a consensus ranking strategy. Network analysis and phenotypic anchoring of the transcriptomic data could discriminate the two diseases at the molecular level. Furthermore, the adjusted IFD protocol was able to recapitulate the binding specificity of potential drug candidates to mutated 3D structures, revealing the relevant amino acids. Importantly, a list of potential drug candidates for repositioning was identified including 61 for NS and 43 for LS and was further verified from literature reports and on-going clinical trials. Altogether, this hybrid computational drug repositioning approach has highlighted a number of drug candidates for NS and LS and could be applied to identifying drug candidates for other diseases as well.

On split involutive regular BiHom-Lie superalgebras

Abstract The goal of this paper is to examine the structure of split involutive regular BiHom-Lie superalgebras, which can be viewed as the natural generalization of split involutive regular Hom-Lie algebras and split regular BiHom-Lie superalgebras. By developing techniques of connections of roots for this kind of algebras, we show that such a split involutive regular BiHom-Lie superalgebra L {\mathfrak{L}} is of the form L = U + ∑ α I α {\mathfrak{L}}=U+{\sum }_{\alpha }{I}_{\alpha } with U a subspace of a maximal abelian subalgebra H and any I α , a well-described ideal of L {\mathfrak{L}} , satisfying [I α , I β ] = 0 if [α] ≠ [β]. In the case of L {\mathfrak{L}} being of maximal length, the simplicity of L {\mathfrak{L}} is also characterized in terms of connections of roots.

Targeted therapy based on germline analysis of tumor-normal sequencing (MSK-IMPACT) in a pan-cancer population.

1500 Background: Tumor mutational profiling for identification of somatic alterations for targeted treatment is increasingly being performed in advanced cancer patients (pts). We sought to assess the clinical utility of germline mutation profiling for targeted therapeutic interventions in a pan-cancer patient population. Methods: All pts who had germline genetic testing through a prospective protocol via a next-generation sequencing panel (MSK-IMPACT) were identified (N=11,975) from 2015-5/2019. The medical record of pts with likely pathogenic/pathogenic germline (LP/P) alterations in genes with known therapeutic targets were reviewed to identify germline-targeted treatment either in a clinical or research setting. Results: We identified 2,043 (17.1%) pts who harbored LP/P variants in a cancer predisposition genes including 777 (6.5%) in genes with potentially targetable therapeutic implications: 416 BRCA1/2, 149 DNA mismatch repair genes (Lynch syndrome, LS), 122 ATM, 45 PALB2, 26 RAD51C/D, 7 RET, 4 TSC, 3 PTCH1, 2 ALK, 1 EGFR, 1 MET and 1 KIT. Of those with advanced disease (n=554), 45.3% received targeted therapeutic treatment (Table) including 50.9% BRCA1/2, 58.3% LS (67.4% of microsatellite-high LS cases), 41.7% PALB2, 36.8% RAD51C/D and 19.3% ATM carriers. Of patients receiving a poly (ADP-ribose) polymerase inhibitor (PARP-I) in the setting of a BRCA1/2 mutation, 55.1% had breast or ovarian cancer; however, 44.8% had other tumors, including pancreas, prostate, bile duct, gastric, wherein the drug was given in a research setting. Among PALB2 pts receiving PARP-Is, 53.3% (8/15) had breast or pancreas cancer; 46.7% had cancer of the prostate, ovary or unknown primary. Conclusions: In our pan-cancer analysis, 6.5% of pts harbored a targetable germline variant highlighting the importance of germline analysis in advanced cancer pts for selection of both FDA-approved treatments and clinical trial participation with germline-targeted therapeutics. [Table: see text]

A rare case of Achromobacter Xylosoxidans infection presenting as Lemierre&amp;apos;s syndrome complicated with bilateral lung empyema in a young boy

Background: In the recent decades, Lemierre\&amp;apos;s syndrome (LS) has been increasingly diagnosed with a wide range of causative organisms, especially with increased awareness of such an entity. Case Presentation: We report an unusual case of LS in a previously healthy 15-year-old boy who presented initially with high grade fever, nonspecific gastrointestinal symptoms, and unilateral purulent otorrhea. Patient subsequently deteriorated requiring intensive care and exhibited altered mental status prompting an urgent contrast enhanced computed tomography brain which clinched the diagnosis. Patient underwent mastoidectomy followed by IV antibiotics that were streamlined according to his pus culture. He also developed bilateral lung empyema requiring bilateral chest tube drainage. Anticoagulation was commenced for the thrombosis and patient was discharged home well. Conclusion: This was an intriguing case in view of the unusual organism causing LS, initial diagnostic dilemma, and challenges in management.

Clinical application of Tunnel-Plasty on modified pedicle subtraction osteotomy

Objective To summarize the technical points and clinical efficacy of pedicle subtraction osteotomy (PSO) in tunneling and to explore the related complications of this technique. Methods A total of 67 cases of old vertebral fractures of the thoracolumbar region from June 2012 to June 2017 were collected. According to the inclusion and exclusion criteria, a total of 41 cases were included in the study. There were 19 males and 22 females; aged 37-67 years, mean 60.1±12.7 years; 15 cases of non-surgical treatment after trauma, 13 cases of failure after surgery and 13 cases of osteoporosis. Injury segment: 9 cases of T11, 22 cases of T12, 8 cases of L1, 2 cases of LS. Preoperative patients were diagnosed by X-ray, CT plain and 3D reconstruction combined with MRI. There were 23 cases of intractable back pain, 16 cases of lower extremity root pain, and 2 cases of intermittent claudication. Patients were divided into the traditional PSO treatment group (21 cases) and modified PSO treatment group (20 persons) according to the random number method. The traditional group were treated with the egg shell technique, and the improved group were treated with tunnel forming technology. The procedure was divided into four steps: exposure (step 1), nail placement and resection of the posterior column complex (step 2), vertebral osteotomy (step 3), orthopedics and bone grafting (step 4). The operation time, bleeding volume and complications of each step were compared between the two groups. The clinical efficacy was evaluated using the visual analogue scale (VAS) score and the Oswestry disability index (ODI). The X-ray spine Cobb angle was measured to evaluate the Keloid deformity correction, and the bone graft fusion was observed by CT examination. Results All patients were followed up for 12 to 24 months. The total operation time of the traditional group was 273.3±21.1 min, and the total operation time of the modified group was 178.1±12.5 min, the difference between the two groups was statistically significant (t=8.981, P=0.0019). The differences between the two groups in steps 2 and 3 were statistically significant (t2=4.614, P2=0.036; t3=9.089, P3=0.020) . The difference in the total bleeding volume was statistically significant (t=8.529, P=0.011). The differences in the bleeding volume between the two groups in step 2 and step 3 were statistically significant (t2=11.933, P2=0.016; t3=6.972, P3=0.013). The Cobb angles of the traditional group before surgery, 1 week after surgery and half year after surgery were 40.2°±8.9°, 12.5°±6.8°, 10.4°±2.5°, respectively. The Cobb angles of the modified group before surgery, 1 week after operation and half year after surgery were 39.5°±6.3°, 10.4°±3.5°, 9.5°±1.9°, respectively. The differences in the Cobb angle between the preoperative, postoperative 1 week and postoperative half year were statistically significant(Fmodified group=189.573, Pmodified group=0.021; Ftraditional group=194.699, Ptraditional group=0.029). The bone fusion time in the osteotomy area was 3-6 months, with an average of 4.8 months. The VAC and ODI scores of half-year post operation of the traditional group were 2.1±0.3 and 34.1±4.3, and the improved group were 2.2±1.1 and 28.3±6.8, respectively, and the difference was not statistically significant. In the improved group, there were 1 case of over-excavation and 1 case of over-underexcavation (2/20), which were corrected in time during operation. In the traditional group, 4 cases (4/21) of dural tear occurred during the operation, and were repaired in time. Bone fusion was obtained half a year later. No clinical deaths, and no cases of surgical infection occured. Conclusion Tunnel forming technology is an alternative surgical procedure for treating old fractures of the thoracolumbar region with PSO, which can shorten the operation time, reducd intraoperative bleeding and reduce surgical complications. Key words: Osteotomy; Orthopedic procedures; Spinal fractures

Scheduling Mutual Exclusion Accesses in Equal-Length Jobs

A fundamental problem in parallel and distributed processing is the partial serialization that is imposed due to the need for mutually exclusive access to common resources. In this article, we investigate the problem of optimally scheduling (in terms of makespan) a set of jobs, where each job consists of the same number L of unit-duration tasks, and each task either accesses exclusively one resource from a given set of resources or accesses a fully shareable resource. We develop and establish the optimality of a fast polynomial-time algorithm to find a schedule with the shortest makespan for any number of jobs and for any number of resources for the case of L = 2. In the notation commonly used for job-shop scheduling problems, this result means that the problem J | d ij =1, n j =2| C max is polynomially solvable, adding to the polynomial solutions known for the problems J 2 | n j ≤ 2 | C max and J 2 | d ij = 1 | C max (whereas other closely related versions such as J 2 | n j ≤ 3 | C max , J 2 | d ij ∈ { 1,2} | C max , J 3 | n j ≤ 2 | C max , J 3 | d ij =1 | C max , and J | d ij =1, n j ≤ 3| C max are all known to be NP-complete). For the general case L &gt; 2 (i.e., for the job-shop problem J | d ij =1, n j = L &gt; 2| C max ), we present a competitive heuristic and provide experimental comparisons with other heuristic versions and, when possible, with the ideal integer linear programming formulation.

Leishmaniasis in Eurasia and Africa: geographical distribution of vector species and pathogens.

Leishmaniasis is a vector-borne disease with a broad global occurrence and an increasing number of recorded cases; however, it is still one of the world's most neglected diseases. We here provide climatic suitability maps generated by means of an ecological niche modelling approach for 32 Phlebotomus vector species with proven or suspected vector competence for five Leishmania pathogens occurring in Eurasia and Africa. A GIS-based spatial overlay analysis was then used to compare the distributional patterns of vectors and pathogens to help evaluate the vector species–pathogen relationship currently found in the literature. Based on this single factor of vector incrimination, that is, co-occurrence of both vector and pathogen, most of the pathogens occurred with at least one of the associated vector species. In the case of L. donovani, only a not yet confirmed vector species, P. rodhaini, could explain the occurrence of the pathogen in regions of Africa. Phlebotomus alexandri and P. longiductus on the other hand, proven vector species of L. donovani, do not seem to qualify as vectors for the pathogen. Their distribution is restricted to northern latitudes and does not match the pathogen's distribution, which lies in southern latitudes. Other more locally confined mismatches were discussed for each pathogen species. The comparative geographical GIS-overlay of vector species and pathogens functions as a first indication that testing and re-evaluation of some pathogen–vector relationships might be worthwhile to improve risk assessments of leishmaniasis.