Contiguous Gene Syndromes and Hearing Loss: A Clinical Report of Xq21 Deletion and Comprehensive Literature Review.

Given the crucial role of the personalized management and treatment of hearing loss (HL), etiological investigations are performed early on, and genetic analysis significantly contributes to the determination of most syndromic and nonsyndromic HL cases. Knowing hundreds of syndromic associations with HL, little comprehensive data about HL in genomic disorders due to microdeletion or microduplications of contiguous genes is available. Together with the description of a new patient with a novel 3.7 Mb deletion of the Xq21 critical locus, we propose an unreported literature review about clinical findings in patients and their family members with Xq21 deletion syndrome. We finally propose a comprehensive review of HL in contiguous gene syndromes in order to confirm the role of cytogenomic microarray analysis to investigate the etiology of unexplained HL.

Microdeletion 1p32p31 Presenting with Moyamoya Disease and Incomplete Hippocampal Inversion.

Background: The chromosome 1p32p31 deletion syndrome is a contiguous gene disorder with a variable phenotype characterized by brain malformations with or without urinary tract defects, besides neurodevelopmental delay and dysmorphisms. An expanded phenotype was proposed based on additional findings, including one previous report of a patient presenting with moyamoya disease. Case Presentation: The authors report a patient presenting with early neurodevelopmental delay, hydrocephalus, renal malformation, and dysmorphisms. After presenting with a sudden choreic movement disorder, the neuroimaging investigation revealed an ischemic stroke, moyamoya disease, and bilateral incomplete hippocampal inversion. Chromosomal microarray analysis revealed a deletion of 13.2 Mb at 1p31.3p32.2, compatible with the contiguous gene syndrome caused by microdeletions of this region. Discussion/Conclusion: This is the second report of a patient who developed Moyamoya disease and the first to describe bilateral incomplete hippocampal inversion in this microdeletion syndrome.

Impact of livelihood capital and rural site conditions on livelihood resilience of farm households: evidence from contiguous poverty-stricken areas in China.

Farm households around the world are increasingly exposed to both external and internal shocks and stressors. Enhancing the resilience of farm households to frequent disturbances holds paramount importance in fostering the sustainability of their livelihoods and the revitalization of rural areas. Based on 1500 household samples from 14 contiguous poverty-stricken areas (CPSA) in China, this study explores the causal pathways between livelihood capitals of farm households and rural site conditions of rural communities, as well as quantifying their impacts on farm households' livelihood resilience using structural equation models. In particular, the livelihood resilience of farm households is measured based on the "Exposure-Sensitivity-Adaptability" framework. The results show that livelihood resilience is positively represented by exposure and adaptability, but is negatively correlated with sensitivity. Specifically, households with lower mean health and higher dependency ratio are more sensitive to risks, while exposure to agroforestry pests and diseases will lead farm households to diversify their livelihood activities and increase crop and livestock variety to enhance their adaptability. The livelihood capital of farm households has a significant positive effect on livelihood resilience (ß = 0.874, p < 0.001). Rural site conditions have both significant direct and indirect impacts on livelihood resilience, with the direct impact (ß = - 0.207, p < 0.05) being negative and a bit larger than the positive indirect impact (ß = 0.163, p < 0.05), as mediated by livelihood capital. The government should, therefore, invest more in health insurance, education and training, financial support, and infrastructure, and implement village planning to enhance both the quality of household livelihood capitals and rural site conditions in CPSA.

Non-contiguous Rare Presentation of Spinal Tuberculosis: A Case Report.

Spinal tuberculosis (TB), also known as Pott's disease, is a severe form of extrapulmonary TB that affects the vertebral bodies and intervertebral discs. While the typical presentation involves the contiguous involvement of multiple vertebrae, atypical forms, such as non-contiguous multilevel spinal TB (NMLST), can occur. However, diagnosing spinal TB poses challenges due to its gradual onset, nonspecific symptoms, and varying imaging results. The timely diagnosis and treatment of spinal TB are critical to prevent serious consequences, including vertebral damage, irreversible neurological impairment, or even death. In this report, we present the case of a 58-year-old South Asian female who presented with several months of back pain, fatigue, and weight loss. Despite initially negative TB test results, spinal magnetic resonance imaging (MRI) raised suspicion of NMLST, which was later confirmed by bone biopsy. This case highlights the complexities of diagnosing and managing atypical spinal TB presentations while discussing the case findings and reviewing relevant research.

The impact of urban irrigation on the temperature-carbon feedback in U.S. cities.

Urban areas experience numerous environmental challenges, among which the anthropogenic emissions of heat and carbon are two major contributors, the former is responsible for the notorious urban heat effect, the latter longterm climate changes. Moreover, the exchange of heat and carbon dioxide are closely interlinked in the built environment, and can form positive feedback loops that accelerate the degradation of urban environmental quality. Among a handful countermeasures for heat and carbon mitigation, urban irrigation is believed to be effective in cooling, yet the understanding of its impact on the co-evolution of heat and carbon emission remains obscure. In this study, we conducted multiphysics urban climate modeling for all urban areas in the contiguous United States, and evaluated the irrigation-induced cooling and carbon mitigation. Furthermore, we assessed the impact of urban irrigation on the potential heat-carbon feedback loop, with their strength of coupling quantified by an advanced causal inference method using the convergent cross mapping algorithms. It is found that the impact of urban irrigation varies vastly in geographically different cities, with its local and non-local effect unraveling distinct pathways of heat-carbon feedback mechanism.

Data on vegetation across forest edges from the FERN (Forest Edge Research Network).

Many studies have focused on vegetation across forest edges to study impacts of edges created by human activities on forest structure and composition, or patterns of vegetation at inherent natural edges. Our objective was to create a database of plant-related variables across different types of edges from various studies (mainly from across Canada, but also in Brazil and Belize) to facilitate edge research. We compiled data on vegetation along more than 300 transects perpendicular to forest edges adjacent to clear-cuts, burned areas, bogs, lakes, barrens, insect disturbances, and riparian areas from 24 studies conducted over the past three decades. Data were compiled for more than 400 plant species and forest structure variables (e.g., trees, logs, canopy cover). All data were collected with a similar sampling design of quadrats along transects perpendicular to forest edges, but with varying numbers of transects and quadrats, and distances from the edge. The purpose for most of the studies was either to determine the distance of edge influence (edge width) or to explore the pattern of vegetation along the edge to interior gradient. We provide data tables for the cover of plant species and functional groups, the species and size of live and dead trees, the density of saplings, maximum height of functional groups and shrub species, and the cover of functional groups at different heights (vertical distribution of vegetation). The Forest Edge Research Network (FERN) database provides extensive data on many variables that can be used for further study including meta-analyses and can assist in answering questions important to conservation efforts (e.g., how is distance of edge influence from created edges affected by different factors?). We plan to expand this database with subsequent studies from the authors and we invite others to contribute to make this a more global database. The data are released under a CC0 license. When using these data, we ask that you cite this data paper and any relevant publications listed in our metadata file. We also encourage you to contact the first author if you are planning to use or contribute to this database.

A Rare Contiguous Gene Deletion Leading to Trichothiodystrophy Type 4 and Glutaric Aciduria Type 3.

Introduction: Trichothiodystrophy type 4 and glutaric aciduria type 3 are rare autosomal recessive disorders caused by biallelic variants in the MPLKIP and SUGCT genes on chromosome 7p14, respectively. Trichothiodystrophy type 4 is characterized by neurologic and cutaneous abnormalities. Glutaric aciduria type 3 is a rare metabolic disorder with inconsistent phenotype and elevated urinary excretion of glutaric acid. Case Presentation: Here, we report on an infant presenting with hypotonia, failure to thrive, microcephaly, dysmorphic features, brittle hair, hypertransaminasemia, and recurrent lower respiratory tract infections. Microarray analysis revealed a homozygous microdeletion involving the MPLKIP and SUGCT genes, which are located close to each other. Conclusion: Copy number variations should be considered in patients with coexisting clinical expression of different genetic alterations. To the best of our knowledge, our patient is the second case with co-occurrence of trichothiodystrophy type 4 and glutaric aciduria type 3, resulting from a contiguous gene deletion.

Xp21 contiguous gene deletion syndrome presenting as Duchenne muscular dystrophy and glycerol kinase deficiency associated with intellectual disability: case report and review literature.

The contiguous gene deletion syndromes (CGDS) are rare genomic disorders resulting from the deletion of large segments of DNA, manifested as the concurrence of apparently unrelated clinical features. A typical example of CGDS is Xp21 contiguous gene deletion syndrome that involves GK and its neigh-boring genes (usually DMD and NR0B1) and results in a complex phenotype, which is related to the size of deletion and involved genes. Development delay and intellectual disability are almost a constant feature of patients with CGDS. We report the case of a boy with Duchenne muscular dystrophy (DMD) and glycerol kinase deficiency (GKD) as part of the contiguous gene deletion syndrome Xp2.1, in association with intellectual disability (ID) in whom multiplex ligation-dependent probe amplification (MLPA) test first identified a hemizygous deletion involving the entire dystrophin gene. Subsequently, the array CGH study identified a maternally inherited hemizygous deletion of the Xp21.2-Xp21.1 region of approximately 3.7Mb that included both DMD and GK genes confirming the diagnosis of Xp21 CGDS. Moreover, we report a review of the cases published in the literature over the last 20 years, for which a better description of the genes involved in the syndrome was available. Intellectual disability does not appear as a constant feature of the syndrome, reiterating the concept that complex GKD syndrome results from small deletions that affect closely related but separate loci for DMD, GK and adrenal hypoplasia, rather than a single large deletion including all genes. This case highlights the importance of more in-depth genetic investigations in presence of apparently unrelated clinical findings, allowing an accurate diagnosis of contiguous gene deletion syndromes.

On univariate optimal partitioning by complete enumeration.

Partitioning a set of elements into a given number of classes to find a globally optimal solution can be challenging due to the combinatorial explosion of the problem size. In the univariate case, where elements can be ordered, the number of partitions is significantly lower than in the multivariate case, and the problem is easier to handle. In this article, we focus on the univariate case and propose using complete enumeration to find a globally optimal solution. Although complete enumeration may also be computationally prohibitive as the number of elements and classes increases, it can be feasible in some situations. For such cases, we propose an algorithm that generates all contiguous partitions for a variable number of classes to be used with any objective function or set of constraints.•We compare exact problem sizes and approximate time complexities for multivariate and univariate partitioning.•We fill a technical gap in the literature by providing a valuable tool for researchers or engineers who need to exactly solve unusual univariate partitioning problems.•We use a convenient data structure for representing partitions of elements into classes and an iterative algorithm that simulates nested loops for any depth level, allowing for efficient generation of all possible contiguous partitions.

Silence, Second Skin, and the Unrepresented.

Using the concepts of microdialect and second skin, this paper explores the idea that a patient's silence in the session may function at multiple levels of psychic and relational organization, and-by virtue of its somatically experienced qualities and the special countertransference states these may elicit-might serve as a vehicle for movement between levels. It can thus be fruitfully approached as a potential portal for access to, and creative transformation of, unrepresented experience.

Non-contiguous multilevel spinal tuberculosis: A case report of unusual spinal tuberculosis resembling spinal metastasis.

Spinal tuberculosis (TB) is diagnostically challenging, particularly in atypical forms. Non-contiguous multilevel spinal TB (NMLST) is a rare presentation of spinal TB, mimicking spinal malignancies. We reported an unusual NMLST case with a paraspinal and epidural abscess in a young patient with misleading clinical and imaging presentations.

Splenic Abscess: A Rare Complication of Bacterial Pneumonia.

Splenic abscess is a rare condition with potentially life-threatening evolution. Hematogenous spread is the most common cause of splenic abscess. Contiguous spread after bacterial pneumonia has rarely been reported in the literature. Early diagnosis can be made by a combination of imaging modalities and clinical features. The successful management of splenic abscess includes timely medical therapy, computed tomography (CT)-guided percutaneous aspiration, and splenectomy. In this report, we discuss a rare case of splenic abscess after hospitalization for bacterial pneumonia. The aim of this case report is to raise awareness about this rare complication so that prompt and appropriate management can be quickly performed to prevent severe outcomes.

The Importance of Genetic Testing in the Differential Diagnosis of Atypical TSC2-PKD1 Contiguous Gene Syndrome-Case Series.

BACKGROUND: In clinical practice, the possible diagnosis of tuberous sclerosis or polycystic kidney disease is primarily based on clinical criteria, which can later be verified by genetic testing. But in the case of TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1-CGS), the renal appearance of the disease is more serious. Therefore, early genetic analysis is recommended. METHODS: Herein we present the report of four children with TSC2/PKD1-CGS, one involving the NTHL1 gene. We aim to emphasize the importance of genetic testing in this rare syndrome. RESULTS: During the follow-up of tuberous sclerosis and polycystic kidney disease patients, it is essential to reappraise the diagnosis if the clinical symptoms' appearance or onset time is unusual. Targeted genetic testing is recommended. However, early tumor formation necessitates the extension of genetic analysis. CONCLUSIONS: An appropriate evaluation of the phenotype is the cornerstone of diagnosing the rare TSC2/PKD1-CGS with the help of genetic results. In addition, malignant tumors could draw attention to an infrequent large deletion.

TSC2/PKD1 contiguous deletion syndrome in a pregnant woman: A case report.

TSC2/PKD1 contiguous gene deletion syndrome is a disease caused by the deletions of the TSC2 and PKD1 genes. This is a rare contiguous genomic disease with clinical manifestations of tuberous sclerosis and polycystic kidney disease. To our knowledge, this case report is the first known case of TSC2/PKD1 contiguous gene deletions in a pregnant woman. The patient had multiple renal cysts, angiomyolipoma, hypomelanotic macules, shagreen patch, subependymal giant cell astrocytoma, multiple cortical tubers, and subependymal nodules. The patient underwent genetic testing. To exclude genetic defects in the fetus, prenatal fetal genetic testing was performed after obtaining the patient's consent. We found an increasing trend in the size of renal cysts and renal angiomyolipomas in patients with polycystic kidney with tuberous sclerosis during pregnancy. Through enhanced clinical monitoring of patients and prenatal genetic testing of the fetus, timely and effective clinical intervention for the mother may be achieved, thus obtaining the best possible outcome for both mother and fetus.

The genetic landscape of autosomal dominant polycystic kidney disease in Kuwait.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal monogenic disease, characterized by bilateral accumulation of renal fluid-filled cysts leading to progressive renal volume enlargement and gradual impairment of kidney function, often resulting in end-stage renal disease. Kuwait could provide valuable genetic insights about ADPKD, including intrafamilial phenotypic variation, given its large household size. This study aims to provide a comprehensive description of the pathogenic variants linked to ADPKD in the Kuwaiti population using multiple genetic analysis modalities and to describe and analyse the ADPKD phenotypic spectrum in terms of kidney function, kidney volume and renal survival. Methods: A total of 126 ADPKD patients from 11 multiplex families and 25 singletons were recruited into the study. A combination of targeted next-generation sequencing (tNGS), long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification were utilized for genetic diagnosis. Clinical evaluation was conducted through renal function testing and ultrasonographic kidney volume analysis. Results: We identified 29 ADPKD pathogenic mutations from 36 families achieving an overall molecular genetic diagnostic rate of 112/126 (88.9%), including 29/36 (80.6%) in families. A total of 28/36 (77.8%) families had pathogenic mutations in PKD1, of which 17/28 (60.7%) were truncating, and 1/36 (2.8%) had a pathogenic variant in the IFT140 gene. A total of 20/29 (69%) of the identified ADPKD mutations were novel and described for the first time, including a TSC2-PKD1 contiguous syndrome. Clinical analysis indicated that genetically unresolved ADPKD cases had no apparent association between kidney volume and age. Conclusion: We describe for the first time the genetic landscape of ADPKD in Kuwait. The observed genetic heterogeneity underlining ADPKD along with the wide phenotypic spectrum reveal the level of complexity in disease pathophysiology. ADPKD genetic testing could improve the care of patients through improved disease prognostication, guided treatment and genetic counselling. However, to fulfil the potential of genetic testing, it is important to overcome the hurdle of genetically unresolved ADPKD cases.

New insights on partial trisomy 3q syndrome: de novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception.

BACKGROUND: Duplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements. CASE PRESENTATION: Hereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth. CONCLUSIONS: Advanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications.

Modularity maximization to design contiguous policy zones for pandemic response.

The health and economic devastation caused by the COVID-19 pandemic has created a significant global humanitarian disaster. Pandemic response policies guided by geospatial approaches are appropriate additions to traditional epidemiological responses when addressing this disaster. However, little is known about finding the optimal set of locations or jurisdictions to create policy coordination zones. In this study, we propose optimization models and algorithms to identify coordination communities based on the natural movement of people. To do so, we develop a mixed-integer quadratic-programming model to maximize the modularity of detected communities while ensuring that the jurisdictions within each community are contiguous. To solve the problem, we present a heuristic and a column-generation algorithm. Our computational experiments highlight the effectiveness of the models and algorithms in various instances. We also apply the proposed optimization-based solutions to identify coordination zones within North Carolina and South Carolina, two highly interconnected states in the U.S. Results of our case study show that the proposed model detects communities that are significantly better for coordinating pandemic related policies than the existing geopolitical boundaries.

Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases.

BACKGROUND: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. AIMS: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. MATERIALS AND METHODS: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. RESULTS: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. LIMITATIONS: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. CONCLUSION: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

A Case Report of Tuberous Sclerosis and Autosomal Dominant Polycystic Kidney Disease in the Era of Tolvaptan.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) may coexist with other genetic disorders, such as tuberous sclerosis, when deletion in TSC2/PKD1 genes occurs. Recently, the effect of tolvaptan has been explored in ADPKD patients alone, but its safety and efficacy on TSC2/PKD1 contiguous gene syndrome are unknown. CASE PRESENTATION: This report describes the case of an asymptomatic patient with TSC2/PKD1 contiguous gene syndrome that fulfills the imaging criteria for initiating the treatment with tolvaptan. After twelve months, the patient did not exhibit severe adverse effects and blood pressure control improved. CONCLUSION: In this TSC2/PKD1 contiguous gene syndrome single case report, tolvaptan was safe and well-tolerated. More extensive experimental studies are needed to deeply understand the therapeutic implications of vasopressin V2-receptor inhibition in the TSC2/PKD1 contiguous gene syndrome patients.

Synthesis of a Dicyclohepta[a,g]heptalene-Containing Polycyclic Conjugated Hydrocarbon and the Impact of Non-Alternant Topologies.

Incorporating non-hexagonal rings into polycyclic conjugated hydrocarbons (PCHs) can significantly affect their electronic and optoelectronic properties and chemical reactivities. Here, we report the first bottom-up synthesis of a dicyclohepta[a,g]heptalene-embedded PCH (1) with four continuous heptagons, which are arranged in a "Z" shape. Compared with its structural isomer bischrysene 1 R with only hexagonal rings, compound 1 presents a distinct antiaromatic character, especially the inner heptalene core, which possesses clear antiaromatic nature. In addition, PCH 1 exhibits a narrower highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy gap than its benzenoid contrast 1 R, as verified by experimental measurements and theoretical calculations. Our work reported herein not only provides a new way to synthesize novel PCHs with non-alternant topologies but also offers the possibility to tune their electronic and optical properties.