bluuebunny/crossref_metadata_2025 huggingface dataset:
Insects Associated with Moringa and their Correlation with Abiotic Parameters
Authors: Yadav Anita , Kumawat M.M. , Ram D. , Pradhan Piyush , Yadav Tara
Published: November 2024

The association of different insect pests and natural enemies was observed on moringa and their correlation with abiotic parameters also recorded at College of Agriculture, Jodhpur during 2023-24. Among the sixteen insect species leaf eating caterpillar, Noorda blitealis Walker was found prominent pest and cause great damage of moringa. The infestation of leaf eating caterpillar started from the first week of July with 3.60 larvae per branch and reached to peak at first week of August with 9.10 larvae per branch. July and August month was more compatible for damage of leaf eating caterpillar. Maximum population of whitefly, leaf-footed bug and ash weevil was observed at last week of October with 59.13 whitefly per 3 branches, first week of November with 3.87 bug per 3 branches and at first week of September with 0.12 weevil per 5 branches, respectively. Among the natural enemies, lady bird beetles were observed as a major predator against aphid and preying mantid preys upon leaf eating caterpillar.
Low-cost Biochar from Parthenium Hysterophorus for Efficient Cr⁶⁺ Removal: A Sustainable Wastewater Treatment Solution
Authors: Naudiyal Nishtha , Srivastava R K
Published: November 2024

Aims: This study explores the development of innovative, cost-effective methods for removing Cr6+ from wastewater, focusing on biochar derived from Parthenium hysterophorus shoots. The biochar was prepared using a conventional slow-pyrolysis process and evaluated for its potential to treat Cr⁶⁺ in aqueous solutions.
Study Design:  Batch adsorption experiments are carried out in the study. 
Place and Duration of Study: The study was conducted in the Department of Environmental Science, G B Pant University of Agriculture & Technology, between Feb 2024 and July 2024.
Methodology: Parthenium hysterophorus shoots were collected, reagents were purchased from HiMedia, and Cr⁶⁺ solutions were prepared and adjusted using NaOH and HCl. Shoots were washed, sun-dried, ground into powder and pyrolysed at 350°C for 180 minutes. Biochar yield was calculated, pH, proximal parameters (moisture, volatile matter, ash, fixed carbon) and ultimate analysis were measured, chemical functional groups by FTIR and morphology by XRD using Bruker D8 Advance was done. Cr⁶⁺ removal was studied using biochar adsorbent under varying pH, initial Cr6+ concentration, adsorbent dose and contact time, adsorption capacity (q) and removal percentage were then calculated.
Results: Characterization techniques such as Fourier Transform Infrared (FTIR) spectroscopy and X-Ray Diffraction (XRD) confirmed the presence of multiple functional groups and crystalline structures, which contribute to its adsorption efficiency. Batch adsorption experiments were conducted to investigate the influence of prepared biochar dosage, initial Cr⁶⁺ concentration, pH and contact time. The optimal removal efficiency of 72.77% was achieved under conditions of pH 10, a biochar dose of 1 g/L, an initial Cr⁶⁺ concentration of 30 mg/L and a contact time of 72 hours.
Conclusion: Although challenges remain in optimizing production and functionalization, this research highlights the potential of biochar for sustainable water treatment. Addressing production costs and practical challenges will further enhance its applicability, contributing to environmental sustainability efforts.
The Role of Plants Having Antimicrobial Properties in the Management of Mental Health Disorders: A Review
Authors: P. Adeniyi, Grace , O. Igbokwe, Christopher , B. Mahady Gail , A. Adeniyi, Bolanle
Published: November 2024

Millions worldwide suffer from mental health disorders such as depression, anxiety, and schizophrenia, underscoring the need for effective, accessible treatments. While conventional therapies have made strides in managing these conditions, challenges such as side effects and high costs persist. This review explores the therapeutic potential of medicinal plants with antimicrobial properties in addressing mental health disorders as there is an established body of knowledge on the link between the gut and the brain (GBA). The impact of the microbes in the gut on the hormones, neurotransmitters, and immune system to name a few has been seen to interfere with the development of mental illness and alleviation of symptoms. The relevant articles were retrieved for analysis through a comprehensive review of current literature using databases like Google Scholar, Web of Science, PubMed, and keywords like ‘Medicinal plants’ ‘Mental health’ ‘Bioactive compounds’, and the appropriate Boolean operators. The inclusion criteria were relevant to common mental health disorders like depression, anxiety, and schizophrenia, while the exclusion criteria included duplicates, lack of full-text availability, and non-English publications. The bioactive compounds in these plants—such as alkaloids, flavonoids, and terpenoids—were analyzed for their interactions with neurotransmitter systems and contributions to mental well-being. Key medicinal plants with antimicrobial properties, including St. John's wort, ashwagandha, and turmeric, were examined for their impact on mental health. The review also highlights the difficulties in translating traditional knowledge into clinical applications, calling for standardization and ethical considerations. Finally, the potential for drug development using biotechnology to enhance the therapeutic value of these medicinal plants is discussed, offering a promising avenue for future mental health treatments.
Formulation and Evaluation of Colon Specific Meloxicam Microcapsules for the Treatment of Arthritis
Authors: Kavitha K , KS Pavan Kumar , Ashitha  , Taj Yasmeen
Published: November 2024

Objective: The main objective of the current study was to formulate and evaluate meloxicam-loaded microcapsules for colon-specific drug delivery using pH-dependent polymers. The emerging need for developing sustained release NSAIDs to minimize the dosing frequency was the main concern. Consequently, creating an oral sustained release formulation for the treatment of arthritis may be one method to get around this.
Methods: Eudragit RS/RL-100 polymers were used in emulsion solvent evaporation processes to create Meloxicam (MLX) microcapsules. Compatibility tests (FTIR), surface morphology by Scanning Electron Microscopy (SEM), yield, drug content, entrapment efficiency, and in vitro dissolution studies were performed on the produced MLX microcapsules.
Results: There was no interaction between the polymer and MLX, according to the IR spectra. The microcapsules were spherical in nature, which was confirmed by SEM. Normal frequency distribution MLX microcapsules were produced. The maximum drug entrapment efficiency of 94% was attained. The in vitro performance of MLX microcapsules demonstrated that the polymer concentration influenced sustained release. Furthermore, it was observed that the amount of polymer utilized regulated the release of the drug.
Conclusion: Based on the findings, it was concluded that one of the most promising formulation methods for creating colon specific drug delivery systems for the treatment of arthritis is the production of MLX microcapsules.
Digital Literacy Skills among Students in Technical Education and Training (TET) Institutions, Tanzania
Authors: Charles Raphael CRN, , Kipene Visent
Published: November 2024

Digital literacy skills (DLS) are one of the essential factors which facilitate academic and non-academic life. The TET institutions remain relevant and attractive if they apply DLS in this era of the changing world. One of the major beneficiaries of DLS in TET are students. However, little is known about the extent to which the students are equipped with DLS. The particular angle of life in which such students apply DLS is as well not yet established. Therefore, this study evaluated the extent to which the TET students are equipped with DLS; and the angle of life from which the DLS are applied by the given students. The DLS of this study are theoretically grounded from digital literacy indicators for undergraduate students by Techataweewan and Prasertsin (2017). This study used a quantitative approach with a descriptive research design. The data were collected using questionnaires from 500 final-year students of four TET institutions sampled through a stratified random sampling technique. The collected data were analysed using descriptive statistics. The findings indicate that the students acquired operation skills (cognition, invention and presentation) and collaboration skills (teamwork, networking and sharing) to a large extent. On the other hand, the students acquired thinking skills (analysis, evaluation and creativity) and awareness skills (ethics, legal literacy and safeguarding self) to a small extent. Furthermore. The TET institutions should advocate more DLS to their students for them to balance the application in academic and non-academic life.
The cytoplasmic region of the amyloid β‐protein precursor (APP) is necessary and sufficient for the enhanced fast velocity of APP transport by kinesin‐1
Authors: Tsukamoto Maoko , Chiba Kyoko , Sobu Yuriko , Shiraki Yuzuha , Okumura Yuka , Hata Saori , Kitamura Akira , Nakaya Tadashi , Uchida Seiichi , Kinjo Masataka , Taru Hidenori , Suzuki Toshiharu
Published: July 2018

Amyloid β‐protein precursor (APP) is transported mainly by kinesin‐1 and at a higher velocity than other kinesin‐1 cargos, such as Alcadein α (Alcα); this is denoted by the enhanced fast velocity (EFV). Interaction of the APP cytoplasmic region with kinesin‐1, which is essential for EFV transport, is mediated by JNK‐interacting protein 1 (JIP1). To determine the roles of interactions between the APP luminal region and cargo components, we monitored transport of chimeric cargo receptors, Alcα (luminal)–APP (cytoplasmic) and APP (luminal)–Alcα (cytoplasmic). Alcα‐APP is transported at the EFV, whereas APP‐Alcα is transported at the same velocity as wild‐type Alcα. Thus, the cytoplasmic region of APP is necessary and sufficient for the EFV of APP transport by kinesin‐1.
A drug‐repositioning screen for primary pancreatic ductal adenocarcinoma cells identifies 6‐thioguanine as an effective therapeutic agent for TPMT‐low cancer cells
Authors: Kim Inki , Choi Yeon‐Sook , Song Jae Hwi , Choi Eun A , Park Sojung , Lee Eun Ji , Rhee Je‐Keun , Kim Song Cheol , Chang Suhwan
Published: July 2018

Pancreatic cancer is one of the most difficult cancers to cure due to the lack of early diagnostic tools and effective therapeutic agents. In this study, we aimed to isolate new bioactive compounds that effectively kill pancreatic ductal adenocarcinoma (PDAC) cells, but not untransformed, human pancreatic ductal epithelial (HPDE) cells. To this end, we established four primary PDAC cell lines and screened 4141 compounds from four bioactive‐compound libraries. Initial screening yielded 113 primary hit compounds that caused over a 50% viability reduction in all tested PDAC cells. Subsequent triplicate, dose‐dependent analysis revealed three compounds with a tumor cell‐specific cytotoxic effect. We found that these three compounds fall into a single category of thiopurine biogenesis. Among them, 6‐thioguanine (6‐TG) showed an IC50 of 0.39–1.13 μm toward PDAC cells but had no effect on HPDE cells. We propose that this cancer selectivity is due to differences in thiopurine methyltransferase (TPMT) expression between normal and cancer cells. This enzyme is responsible for methylation of thiopurine, which reduces its cytotoxicity. We found that TPMT levels were lower in all four PDAC cell lines than in HPDE or Panc1 cells, and that knockdown of TPMT in HPDE or Panc1 cells sensitized them to 6‐TG. Lastly, we used a patient‐derived xenograft model to confirm that 6‐TG has a significant antitumor effect in combination with gemcitabine. Overall, our study presents 6‐TG as a strong candidate for use as a therapeutic agent against PDAC with low levels of TPMT.
Early Self‐Reported Pain in Juvenile Idiopathic Arthritis as Related to Long‐Term Outcomes: Results From the Nordic Juvenile Idiopathic Arthritis Cohort Study
Authors: Arnstad Ellen Dalen , Rypdal Veronika , Peltoniemi Suvi , Herlin Troels , Berntson Lillemor , Fasth Anders , Nielsen Susan , Glerup Mia , Ekelund Maria , Zak Marek , Aalto Kristiina , Nordal Ellen , Romundstad Pål Richard , Rygg Marite ,   the Nordic Study Group of Pediatric Rheumatology
Published: July 2018

Objective

To study self‐reported pain early in the disease course of juvenile idiopathic arthritis (JIA) as a predictor of long‐term disease outcomes.

Methods

Consecutive cases of JIA with disease onset from 1997 to 2000 from defined geographical areas of Norway, Sweden, Finland, and Denmark were prospectively enrolled in this population‐based cohort study. Self‐reported, disease‐related pain was measured on a 10‐cm visual analog scale (VAS pain). Inclusion criteria were a baseline visit with a pain score 6 months after disease onset, followed by an 8‐year study visit. Remission was defined according to Wallace et al (2004) preliminary criteria. Functional disability was measured by the Childhood Health Assessment Questionnaire and the Child Health Questionnaire Parent Form if the child was age <18 years and by the Health Assessment Questionnaire if age ≥18 years. Damage was scored using the Juvenile Arthritis Damage Index.

Results

The final study cohort consisted of 243 participants, and 120 participants (49%) had oligoarticular onset. At baseline, 76% reported a VAS pain score >0 compared to 57% reporting at 8 years. Half of those who reported baseline pain also reported pain at 8 years but at a lower intensity. Compared to no pain, higher pain intensity at baseline predicted more pain at 8 years, more functional disability, more damage, and less remission without medication. Baseline pain predicted more use of disease‐modifying antirheumatic drugs/biologics during the disease course. Participants with oligoarticular JIA reporting pain at baseline were more likely to develop extended oligoarticular JIA or other JIA categories with an unfavorable prognosis.

Conclusion

Early self‐reported, disease‐related pain among children and adolescents with JIA is common and seems to predict persistent pain and unfavorable long‐term disease outcomes.
Cost‐Effectiveness of Diet and Exercise for Overweight and Obese Patients With Knee Osteoarthritis
Authors: Losina Elena , Smith Karen C. , Paltiel A. David , Collins Jamie E. , Suter Lisa G. , Hunter David J. , Katz Jeffrey N. , Messier Stephen P.
Published: July 2018

Objective

The Intensive Diet and Exercise for Arthritis (IDEA) trial showed that an intensive diet and exercise (D+E) program led to a mean 10.6‐kg weight reduction and 51% pain reduction in patients with knee osteoarthritis (OA). The aim of the current study was to investigate the cost‐effectiveness of adding this D+E program to treatment in overweight and obese (body mass index >27 kg/m2) patients with knee OA.

Methods

We used the Osteoarthritis Policy Model to estimate quality‐adjusted life‐years (QALYs) and lifetime costs for overweight and obese patients with knee OA, with and without the D+E program. We evaluated cost‐effectiveness with the incremental cost‐effectiveness ratio (ICER), a ratio of the differences in lifetime cost and QALYs between treatment strategies. We considered 3 cost‐effectiveness thresholds: $50,000/QALY, $100,000/QALY, and $200,000/QALY. Analyses were conducted from health care sector and societal perspectives and used a lifetime horizon. Costs and QALYs were discounted at 3% per year. D+E characteristics were derived from the IDEA trial. Deterministic and probabilistic sensitivity analyses (PSAs) were used to evaluate parameter uncertainty and the effect of extending the duration of the D+E program.

Results

In the base case, D+E led to 0.054 QALYs gained per person and cost $1,845 from the health care sector perspective and $1,624 from the societal perspective. This resulted in ICERs of $34,100/QALY and $30,000/QALY. In the health care sector perspective PSA, D+E had 58% and 100% likelihoods of being cost‐effective with thresholds of $50,000/QALY and $100,000/QALY, respectively.

Conclusion

Adding D+E to usual care for overweight and obese patients with knee OA is cost‐effective and should be implemented in clinical practice.
Substituting Sedentary Time With Physical Activity in Fibromyalgia and the Association With Quality of Life and Impact of the Disease: The al‐Ándalus Project
Authors: Gavilán‐Carrera Blanca , Segura‐Jiménez Víctor , Mekary Rania A. , Borges‐Cosic Milkana , Acosta‐Manzano Pedro , Estévez‐López Fernando , Álvarez‐Gallardo Inmaculada C. , Geenen Rinie , Delgado‐Fernández Manuel
Published: July 2018

Objective

There is an overall awareness of the detrimental health effects of sedentary time (ST) in fibromyalgia; however, data are limited on how replacement of ST with physical activity (PA) of different intensity may be related to health in this condition. The aim of this study was to examine how a substitution of ST with light PA (LPA) or moderate‐to‐vigorous PA (MVPA) is associated with quality of life and disease impact.

Methods

This study comprised 407 women with fibromyalgia, mean ± SD age 51.4 ± 7.6 years. The time spent in ST and PA was measured with triaxial accelerometry. Quality of life and disease impact were assessed using the Short Form 36 (SF‐36) health survey and the Revised Fibromyalgia Impact Questionnaire (FIQR), respectively. The substitution of ST with an equivalent time of LPA or MVPA and the associated outcomes were examined using isotemporal substitution analyses.

Results

Substituting 30 minutes of ST with LPA in the isotemporal model was associated with better scores in bodily pain (B = 0.55), vitality (B = 0.74), and social functioning (B = 1.45) according to the SF‐36, and better scores at all of the domains (function, overall impact, symptoms, and total impact) of the FIQR (B ranging from –0.95 to –0.27; all P < 0.05). When ST was replaced with MVPA, better physical role (B = 2.30) and social functioning (B = 4.11) of the SF‐36 and function of the FIQR (B = –0.73) were observed (all P < 0.05).

Conclusion

In regression models, allocation of time of sedentary behavior to either LPA or MVPA was associated with better quality of life and lower disease impact in women with fibromyalgia.
The Impact of Belimumab and Rituximab on Health‐Related Quality of Life in Patients With Systemic Lupus Erythematosus
Authors: Parodis Ioannis , Lopez Benavides Angie H. , Zickert Agneta , Pettersson Susanne , Möller Sonia , Welin Henriksson Elisabet , Voss Anne , Gunnarsson Iva
Published: July 2018

Objective

Accumulating evidence supports an impaired health‐related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). We investigated the effects of 2 biologic treatments on HRQoL of patients with SLE.

Methods

Patients with SLE from the Karolinska University Hospital treated with belimumab (n = 34) or rituximab (n = 35) were included; normative values derived from Swedish population‐based controls matched for age and sex were used for the purpose of comparisons. Data were collected prospectively at treatment initiation and at months 3, 6, 12, and 24, using the Short Form 36 (SF‐36) health questionnaire, the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐Fatigue) scale, the EuroQol 5‐dimension (EQ‐5D) instrument, and the Stanford Health Assessment Questionnaire disability index (HAQ DI).

Results

Substantial decrements from Swedish norms were observed across all SF‐36 domains at baseline. Patients treated with belimumab reported gradual improvements in the SF‐36 physical component summary (significant from month 12; P = 0.023) and FACIT‐Fatigue (significant by month 24; P = 0.001), no changes in EQ‐5D scores, and improvements in HAQ DI by month 6 (P = 0.014). Patients treated with rituximab showed rapid improvements in the SF‐36 mental component summary and FACIT‐Fatigue by month 3 (P = 0.031 and P = 0.007, respectively), as well as improvements in EQ‐5D at month 6 (P = 0.016) and HAQ DI at month 3 (P = 0.033). Based on baseline evaluations, patients receiving antimalarial agents (n = 33) performed better in the SF‐36 social functioning (P = 0.022) and mental health (P = 0.023) domains compared to patients who did not receive antimalarial agents (n = 36).

Conclusion

Our results corroborated previous findings of considerable HRQoL impairments in patients with SLE. Patients' perceptions of HRQoL showed discrepant patterns over time in the 2 treatment groups and could provide additional information along with the clinical evaluation of biologic therapy in SLE. Further survey on the effects of antimalarial agents on the HRQoL of patients with SLE in larger cohorts is merited.
Most Important Frequently Asked Questions From Patients With Hip or Knee Osteoarthritis: A Best‐Worst Scaling Exercise
Authors: Claassen Aniek A. O. M. , Kremers–van de Hei Keetie C. A. L. C. , van den Hoogen Frank H. J. , van der Laan Willemijn H. , Rijnen Wim H. C. , Koëter Sander , Botman Joris , Busch Vincent J. J. F. , Schers Henk J. , van den Ende Cornelia H. M.
Published: July 2018

Objective

To collect and prioritize the frequently asked questions (FAQs) that patients with hip or knee osteoarthritis (OA) and health care professionals consider to be the most important; to identify informational needs that go beyond guideline recommendations.

Methods

FAQs were collected among health care professionals and from the arthritis helpline of the Dutch Arthritis Foundation. After deleting overlapping FAQs, the remaining FAQs were prioritized by patients and health care professionals using a maximum difference scaling method. A hierarchical Bayesian method was used to calculate relative importance scores. Differences between health care professionals and patients were analyzed using independent t‐tests.

Results

A total of 28 health care professionals and the arthritis helpline provided 192 FAQs. After deleting overlapping FAQs, 60 FAQs were prioritized by 94 patients (57 [60.6%] women, mean age 67.3 years) and 122 health care professionals (67 [54.9%] women, mean age 45.7 years). The FAQ “What can I do myself to decrease symptoms and to prevent the OA from getting worse?” was prioritized as the most important by both patients and professionals. FAQs that were highly prioritized by patients but significantly different from professionals were more directed toward treatment options offered by health care professionals, whereas highly prioritized FAQs of professionals were more often focused on treatment options involving self‐management.

Conclusion

The health care professionals’ perspective on informational needs differs from that of OA patients. These differences are important to address in order to achieve more active involvement of patients in their own treatment process.
Clinical Remission and Low Disease Activity Outcomes Over 10 Years in Systemic Lupus Erythematosus
Authors: Tselios Konstantinos , Gladman Dafna D. , Touma Zahi , Su Jiandong , Anderson Nicole , Urowitz Murray B.
Published: July 2018

Objective

A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years).

Methods

Patients in the inception cohort of the Toronto Lupus Clinic, who had a minimum follow‐up of 10 years and no interval >18 months between consecutive visits, were included in the analysis. Prolonged clinical remission was defined based on a SLEDAI‐2K score of 0 (serology excluded), achieved within the first 5 years of enrollment and maintained for ≥10 years. Prolonged LDA was defined as SLEDAI‐2K score ≤2 (serology excluded) with the same time frame restrictions.

Results

Of 267 patients, 27 (10.1%) achieved prolonged clinical remission and 48 (18%) attained prolonged LDA. There were no differences regarding demographic, clinical, and immunologic variables at any time. The mean prednisone dose at enrollment was higher in patients in whom remission was achieved, while patients with prolonged LDA were taking antimalarials more frequently, both at enrollment and after the 10‐year time period. Cumulative damage and flare rate after 10 years, and mortality throughout follow‐up were comparable. SLE in patients in the prolonged LDA group was in complete remission for 76% of the follow‐up time.

Conclusion

Prolonged clinical remission and LDA were demonstrated in 10.1% and 18% of our patients, respectively, and comparable outcomes were demonstrated in the long term, rendering sustained LDA an acceptable treat‐to‐target outcome in SLE.
Area‐Level Predictors of Medication Nonadherence Among US Medicaid Beneficiaries With Lupus: A Multilevel Study
Authors: Feldman Candace H. , Costenbader Karen H. , Solomon Daniel H. , Subramanian S. V. , Kawachi Ichiro
Published: July 2018

Objective

Adherence to hydroxychloroquine (HCQ) treatment in patients with systemic lupus erythematous (SLE) is suboptimal. Although individual‐level factors, including younger age and non‐white race/ethnicity, have been implicated, contextual factors have not been explored. The aim of this study was to investigate the effect of contextual factors, including racial composition, socioeconomic status, and the concentration of health care resources, on adherence to HCQ among SLE patients enrolled in Medicaid.

Methods

We identified SLE patients from 28 states in the US who enrolled in Medicaid (2000–2010) and in whom HCQ treatment was newly initiated (no use for ≥6 months). We required 12 months of continuous enrollment with complete drug dispensing data and measured adherence using the proportion of days covered (PDC). We identified individual‐level variables from Medicaid, zip code–level, county‐level and state‐level sociodemographic variables from the American Community Survey, and health resources from Area Health Resources Files. We used 4‐level hierarchical multivariable logistic regression models to examine the odds ratios (ORs) and 95% credible intervals (95% CrIs) of adherence (PDC ≥80%) versus nonadherence.

Results

Among 10,268 patients with SLE in whom HCQ treatment was initiated, 15% were adherent to treatment. After we adjusted for individual‐level characteristics, we observed lower odds of adherence among patients living in zip code areas with a higher percentage of black individuals (highest tertile OR 0.81 [95% CrI 0.69–0.96] versus lowest tertile). This association persisted after controlling for area‐level educational attainment, percent below federal poverty level (FPL), urbanicity, and health care resources. We did not observe statistically significant associations with zip code–level percent Hispanic, percent white, education, or percent below FPL. The odds of adherence were higher in counties with more hospitals (OR 1.30 [95% CrI 1.07–1.58]).

Conclusion

Among Medicaid beneficiaries with SLE, we observed significant effects of racial composition and hospital concentration on HCQ adherence. Interventions that acknowledge and address contextual factors should be considered in order to reduce high rates of nonadherence in vulnerable populations.
Drag of a cylinder moving near a wall in a yield stress fluid
Authors: Ouattara Ziemihori , Jay Pascal , Blésès Didier , Magnin Albert
Published: July 2018

The drag of a cylindrical obstacle moving at a constant velocity in a yield stress fluid close to a wall is studied experimentally and numerically. The wall influence has been explored for gap values between the cylinder of diameter D and the wall ranging from 0.01D to 100D, which corresponds, respectively, to hydrodynamic lubrication and to unconfined domain conditions. A model yield stress fluid (Carbopol gel) is used in the experiments. The viscous and plastic drag coefficients have been calculated and measured as depending on the Oldroyd number, in conditions where the yield stress effects are more important than those of viscosity and the inertia negligible. We have performed experimental and numerical validations in the Newtonian case and provided more specifically comparisons of our measured data on yield stress materials with those resulting from viscoplastic flow simulations. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4118–4130, 2018
Expanding the fetal phenotype: Prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome
Authors: Schindewolf Erica , Khalek Nahla , Johnson Mark P. , Gebb Juliana , Coleman Beverly , Crowley Terrence Blaine , Zackai Elaine H. , McDonald‐McGinn Donna M. , Moldenhauer Julie S.
Published: July 2018

22q deletion syndrome (22q11.2DS) is most often correlated prenatally with congenital heart disease and or cleft palate. The extracardiac fetal phenotype associated with 22q11.2DS is not well described. We sought to review both the fetal cardiac and extracardiac findings associated with a cohort of cases ascertained prenatally, confirmed or suspected to have 22q11.2DS, born and cared for in one center. A retrospective chart review was performed on a total of 42 cases with confirmed 22q11.2DS to obtain prenatal findings, perinatal outcomes and diagnostic confirmation. The diagnosis was confirmed prenatally in 67% (28/42) and postnatally in 33% (14/42). The majority (81%) were associated with the standard LCR22A‐LCR22D deletion. 95% (40/42) of fetuses were prenatally diagnosed with congenital heart disease. Extracardiac findings were noted in 90% (38/42) of cases. Additional findings involved the central nervous system (38%), gastrointestinal (14%), genitourinary (16.6%), pulmonary (7%), skeletal (19%), facial dysmorphism (21%), small/hypoplastic thymus (26%), and polyhydramnios (30%). One patient was diagnosed prenatally with a bilateral cleft lip and cleft palate. No fetus was diagnosed with intrauterine growth restriction. The average gestational age at delivery was 38 weeks and average birth weight was 3,105 grams. Sixty‐two percentage were delivered vaginally and there were no fetal demises. A diagnosis of 22q11.2 deletion syndrome should be considered in all cases of prenatally diagnosed congenital heart disease, particularly when it is not isolated. Microarray is warranted in all cases of structural abnormalities diagnosed prenatally. Prenatal diagnosis of 22q11.2 syndrome can be used to counsel expectant parents regarding pregnancy outcome and guide neonatal management.
De novo KCNA1 variants in the PVP motif cause infantile epileptic encephalopathy and cognitive impairment similar to recurrent KCNA2 variants
Authors: Rogers Amanda , Golumbek Paul , Cellini Elena , Doccini Viola , Guerrini Renzo , Wallgren‐Pettersson Carina , Thuresson Ann‐Charlotte , Gurnett Christina A.
Published: July 2018

Derangements in voltage‐gated potassium channel function are responsible for a range of paroxysmal neurologic disorders. Pathogenic variants in the KCNA1 gene, which encodes the voltage‐gated potassium channel Kv1.1, are responsible for Episodic Ataxia Type 1 (EA1). Patients with EA1 have an increased incidence of epilepsy, but KCNA1 variants have not been described in epileptic encephalopathy. Here, we describe four patients with infantile‐onset epilepsy and cognitive impairment who harbor de novo KCNA1 variants located within the Kv‐specific Pro‐Val‐Pro (PVP) motif which is essential for channel gating. The first two patients have KCNA1 variants resulting in (p.Pro405Ser) and (p.Pro405Leu), respectively, and a set of identical twins has a variant affecting a nearby residue (p.Pro403Ser). Notably, recurrent de novo variants in the paralogous PVP motif of KCNA2 have previously been shown to abolish channel function and also cause early‐onset epileptic encephalopathy. Importantly, this report extends the range of phenotypes associated with KCNA1 variants to include epileptic encephalopathy when the PVP motif is involved.
A recognizable phenotype related to 19p13.12 microdeletion
Authors: de Souza Laiara Cristina , Sgardioli Ilária Cristina , Gil‐da‐Silva‐Lopes Vera Lúcia , Vieira Társis Paiva
Published: July 2018

Submicroscopic deletions in chromosome 19 have been rarely reported. We reported a male patient presenting with neurodevelopmental delay and facial dysmorphisms with a de novo 19p13.11p13.12 deletion of approximately 1.4 Mb. To date, there are seven cases with deletions overlapping the 19p13.11–p13.12 region described in the literature. A region of 800 kb for branchial arch defects in the proximal region of 19p13.12, and another minimal critical region of 305 kb for hypertrichosis, synophrys, and protruding front teeth have been proposed previously. We suggest that the shortest region of overlap could be refined to an approximately 53 kb region shared within all patients, encompassing part of BRD4 and AKAP8L genes and the AKAP8 gene. Based on the genotype‐phenotype correlation of the present case and cases with overlapping deletions described in the literature, it was possible to recognize a consistent phenotype characterized by microcephaly, ear abnormalities, rounded face, synophrys, arched or upwardly angulated eyebrows, short nose, anteverted nares, prominent cheeks, teeth abnormalities, and developmental delay.
Inflammatory facioscapulohumeral muscular dystrophy type 2 in 18p deletion syndrome
Authors: Renard Dimitri , Taieb Guillaume , Garibaldi Matteo , Maues De Paula Andre , Bernard Rafaelle , Lagha Nadira , Cristofari Gael , Vovan Catherine , Chaix Charlène , Lévy Nicolas , Khau Van Kien Philippe , Sacconi Sabrina
Published: July 2018

Facioscapulohumeral muscular dystrophy (FSHD) has been shown to be related to genetic and epigenetic derepression of DUX4 (mapping to chromosome 4), a gene located within a repeat array of D4Z4 sequences of polymorphic length. FSHD type 1 (FSHD1) is associated with pathogenic D4Z4 repeat array contraction, while FSHD type 2 (FSHD2) is associated with SMCHD1 variants (a chromatin modifier gene that maps to the short arm of chromosome 18). Both FSHD types require permissive polyadenylation signal (4qA) downstream of the D4Z4 array.
A 69‐year‐old woman with Coffin–Siris syndrome
Authors: Määttänen Laura , Hietala Marja , Ignatius Jaakko , Arvio Maria
Published: July 2018

Coffin–Siris syndrome (CSS) is a rare intellectual disability syndrome classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and other digits, distinctive facial features, hirsutism/hypertrichosis, and sparce scalp hair. It is genetically heterogeneous but most often caused by a pathogenic variant in the ARID1B gene. Previous clinical reports of CSS patients are mainly based on young or middle‐aged individuals. Here, we report a 69‐year‐old woman with CSS phenotype and a pathogenic ARID1B loss‐of‐function variant c.5259_5260dup. She has severe intellectual disability but otherwise she is in relatively good health both physically and mentally. There is no evident history of chronic illness or progressive disability. CSS appears to be compatible with long survival and most likely it is underdiagnosed in geriatric patients with intellectual disability.
A case of severe TBCE‐negative hypoparathyroidism‐retardation‐dysmorphism syndrome: Case report and literature review
Authors: Ryabets‐Lienhard Anna , Issaranggoon na Ayuthaya Satja , Graham John M. , Pitukcheewanont Pisit
Published: July 2018

Hypoparathyroidism‐retardation‐dysmorphism syndrome (HRD) is a rare autosomal recessive disorder attributed to the mutations in the tubulin‐specific chaperone E (TBCE) gene, which is vital for microtubule function during mitosis, organelle positioning, and neuronal cytokinesis. HRD is a congenital syndromic hypoparathyroidism associated with growth deficiency, microcephaly, intellectual disability, ocular anomalies, and facial dysmorphism. To our knowledge, there is only one published case of mild HRD‐like syndrome with no identifiable genetic etiology. We report a case of severe TBCE‐negative phenotypic HRD in a 4‐year‐old female from India presenting with hypocalcemic seizures due to congenital hypoparathyroidism, extreme microcephaly, growth deficiency, ocular anomalies, and facial dysmorphism. SNP microarray and whole exome sequencing (WES) did not detect any abnormalities in TBCE or other genes of interest. WES revealed two variants of unknown clinical significance in CASC5 gene, which codes for a protein in the kinetochore and, interestingly similar to TBCE, is essential for proper microtubule function during mitosis and cell proliferation and has been implicated in primary microcephaly disorders. However, further targeted sequencing in the parents revealed both variants inherited from the unaffected mother. Significant copy number variant noise in the proband and her parents limited further analysis. At this time the role of variants in the CASC5 gene is unclear and cannot explain our patient's phenotype. In conclusion, we report a severe case of phenotypic HRD syndrome, in which extensive genetic evaluation failed to reveal an etiology. Our case demonstrates that the pathogenesis of HRD may be genetically heterogenous, meriting further genetic investigations.
Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients
Authors: Levin Mark D. , Saitta Sulagna C. , Gripp Karen W. , Wenger Tara L. , Ganesh Jaya , Kalish Jennifer M. , Epstein Michael R. , Smith Rosemarie , Czosek Richard J. , Ware Stephanie M. , Goldenberg Paula , Myers Angela , Chatfield Kathryn C. , Gillespie Matthew J. , Zackai Elaine H. , Lin Angela E.
Published: July 2018

Multifocal atrial tachycardia (MAT) has a well‐known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first‐line supraventricular tachycardia anti‐arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti‐arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4‐month‐old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.
Is exon 8 the most critical or the only dispensable exon of the VCAN gene? Insights into VCAN variants and clinical spectrum of Wagner syndrome
Authors: Ankala Arunkanth , Jain Nieraj , Hubbard Baker , Alexander John J. , Shankar Suma P.
Published: July 2018

Wagner syndrome and erosive vitreoretinopathy together constitute the phenotypic continuum of an autosomal dominant vitreoretinopathy, with clinical findings typically isolated to the eye. The disease is caused by pathogenic variants in the VCAN gene and all such variants reported to date are those that plausibly result in haploinsufficiency of exon 8 containing vcan transcripts. Here, we report the molecular findings and long‐term follow‐up of a 16‐year‐old female with a history of retinal detachments and pigmentary retinal changes. Next‐generation sequencing and microarray analysis of 141 genes established a diagnosis of Wagner syndrome in this individual, by detection of an 11.7 kilobase (kb) deletion encompassing exon 8 of VCAN. In light of the emerging functions and roles of versican protein in human disease, we discuss how variants within exon 8 of the VCAN gene can be compared to those in exon 2 of the COL2A1 gene that cause atypical Stickler syndrome and propose that variants in other regions of the gene can be expected to present with a more systemic disease. The distinctive facial features and atypical gastrointestinal symptoms observed in this long‐term follow‐up study support the possibility that individuals with VCAN‐related vitreoretinopathy may have extra‐ocular clinical features.
De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities, developmental delay, intellectual disability and dysmorphic features
Authors: Douglas Ganka , Cho Megan T. , Telegrafi Aida , Winter Susan , Carmichael Jason , Zackai Elaine H. , Deardorff Matthew A. , Harr Margaret , Williams Linford , Psychogios Apostolos , Erwin Angelika L. , Grebe Theresa , Retterer Kyle , Juusola Jane
Published: July 2018

Gross deletions involving the MEIS2 gene have been described in a small number of patients with overlapping phenotypes of atrial or ventricular septal defects, cleft palate, and variable developmental delays and intellectual disability. Non‐specific dysmorphic features were noted in some patients, including broad forehead with high anterior hairline, arched eyebrows, thin or tented upper lip, and short philtrum. Recently, a patient with a de novo single amino acid deletion, c.998_1000delGAA (p.Arg333del), and a patient with a de novo nonsense variant, (c.611C>G, p.Ser204*), were reported with a similar, but apparently more severe phenotypes. Clinical whole exome sequencing (WES) performed at our clinical molecular diagnostic laboratory identified four additional patients with predicted damaging de novo MEIS2 missense variants. Our patients’ features closely resembled those previously reported in patients with gross deletions, but also included some less commonly reported features, such as autism spectrum disorder, hearing loss, and short stature, as well as features that may be unique to nucleotide‐level variants, such as hypotonia, failure to thrive, gastrointestinal, skeletal, limb, and skin abnormalities. All of the observed missense variants, Pro302Leu, Gln322Leu, Arg331Lys, and Val335Ala, are located in the functionally important MEIS2 homeodomain. Pro302Leu is found in the region between helix 1 and helix 2, while the other three are located in the DNA‐binding helix 3. To our knowledge, these are the first described de novo missense variants in MEIS2, expanding the known mutation spectrum of the newly recognized human disorder caused by aberrations in this gene.
A novel MYT1L mutation in a patient with severe early‐onset obesity and intellectual disability
Authors: Loid Petra , Mäkitie Riikka , Costantini Alice , Viljakainen Heli , Pekkinen Minna , Mäkitie Outi
Published: July 2018

The genetic background of severe early‐onset obesity is still incompletely understood. Deletions at 2p25.3 associate with early‐onset obesity and variable intellectual disability. Myelin‐transcriptor‐factor‐1‐like (MYT1L) gene in this locus has been proposed a candidate gene for obesity. We report on a 13‐year‐old boy presenting with overweight already at 1 year of age (body mass index [BMI] Z‐score +2.3) and obesity at 2 years of age (BMI Z‐score +3.8). The patient had hyperphagia and delayed neurological, cognitive and motor development. He also had speech delay, strabismus, hyperactivity and intellectual disability. Brain MRI was normal. The parents and sister had normal BMI. Whole‐genome sequencing identified in the index patient a novel de novo frameshift deletion that introduces a premature termination of translation NM_015025.2(MYT1L): c.2215_2224delACGCGCTGCC, p.(Thr739Alafs*7) in MYT1L. The frameshift variant was confirmed by Sanger sequencing. Our finding supports the association of MYT1L mutations with early‐onset syndromic obesity. The identification of novel monogenic forms of childhood‐onset obesity will provide insights to the involved genetic and biologic pathways.
Health supervision for people with Bloom syndrome
Authors: Cunniff Christopher , Djavid Amir Reza , Carrubba Steven , Cohen Bernard , Ellis Nathan A. , Levy Carolyn Fein , Jeong Stacy , Lederman Howard M. , Vogiatzi Maria , Walsh Michael F. , Zauber Ann Graham
Published: July 2018

Bloom Syndrome (BSyn) is an autosomal recessive disorder that causes growth deficiency, endocrine abnormalities, photosensitive skin rash, immune abnormalities, and predisposition to early‐onset cancer. The available treatments for BSyn are symptomatic, and early identification of complications has the potential to improve outcomes. To accomplish this, standardized recommendations for health supervision are needed for early diagnosis and treatment. The purpose of this report is to use information from the BSyn Registry, published literature, and expertise from clinicians and researchers with experience in BSyn to develop recommendations for diagnosis, screening, and treatment of the clinical manifestations in people with BSyn. These health supervision recommendations can be incorporated into the routine clinical care of people with BSyn and can be revised as more knowledge is gained regarding their clinical utility.
A recessive truncating variant in thrombospondin‐1 domain containing protein 1 gene THSD1 is the underlying cause of nonimmune hydrops fetalis, congenital cardiac defects, and haemangiomas in four patients from a consanguineous family
Authors: Abdelrahman Hanadi A. , Al‐Shamsi Aisha , John Anne , Hertecant Jozef , Lootah Ali , Ali Bassam R. , Al‐Gazali Lihadh
Published: July 2018

Non‐immune hydrops fetalis (NIHF) is the abnormal accumulation of serous fluid in more than two fetal or neonatal interstitial spaces due to nonimmune causes. It is a serious condition that requires extensive medical care as it indicates severe fetal compromise. We clinically evaluated four patients from two branches of a highly consanguineous family from the UAE with NIHF using whole exome sequencing and in silico analysis. Fetal onset pleural and peritoneal effusions were detected in all four patients and were born with moderate to severe hydrops fetalis that resolved with age. Follow up showed relatively normal growth and development apart from mild ascites and haemangiomas in all affected children, recurrent hydrocele in all affected males, intestinal malabsorption in two patients, dysmorphic features in two patients, and congenital cardiac defects in three out of four patients. Molecular testing identified a homozygous eight nucleotide deletion in THSD1 gene (NM_199263:c.1163_1170delGGCCAGCC, p.Arg388Glnfs*66) as the underlying cause of this phenotype in the affected children. The novel variant cosegregates with the described phenotype in an autosomal recessive mode of inheritance and is predicted to be pathogenic as it leads to a truncated protein that lost important structural and functional domains. Thrombospondin‐1 domain containing protein 1 gene THSD1 has been recently associated with of NIHF and embryonic lethality. Here, we report the novel truncating THSD1 variant, and describe new clinical features that have not been reported previously thus expanding the phenotype associate with loss‐of‐function mutations in THSD1 causing NIHF.