bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel BEST1 mutations and clinical characteristics of autosomal recessive bestrophinopathy in a Spanish patient
Authors: Soto-Sierra Marina , Morillo-Sánchez María José , Martín-Sánchez Marta , Ramos-Jiménez Manuel , López-Domínguez Mireia , Ponte-Zuñiga Beatriz , Antiñolo Guillermo , Rodríguez-de-la-Rúa Enrique 
Published: April 2021

Purpose: To describe the clinical and genetic characteristics (novel mutation in BEST1 gene) of a Spanish patient with autosomal recessive bestrophinopathy (ARB). Methods: The detailed ophthalmological examination included best corrected visual acuity (BCVA), color and autofluorescence photography, fluorescein angiography, optical coherence tomography, and electrophysiology tests. A next-generation sequencing (NGS) strategy was applied to the index patient, and then sequenced in an Illumina NextSeq500 system. Results: A 55-year-old male presented with a BCVA of 20/25 in the right eye and 20/20 in the left eye. Fundoscopy revealed perifoveal yellow flecked-like lesions. Fluorescein angiography and fundus autofluorescence results were consistent with pattern dystrophy. A homozygous frameshift mutation in BEST1 (c.341_342del; p.(Leu114Glnfs*57)) was identified as the cause of the disease. Conclusion: ARB is a genetic disease that leads to irreversible visual loss. In this report we found a novel mutation responsible for this disease.
Safe and effective HeRO graft placement: Technique and results
Authors: Illig Karl A , London Mark J , Aruny John , Ross John R 
Published: April 2021

Objectives: Hemodialysis Reliable Outflow (HeRO) grafts are used when venous outflow is inadequate to support conventional access. These have been perceived as complex to implant and being associated with high risk. We have evolved a defined protocol for insertion that minimizes morbidity and maximizes efficiency. Methods: Our protocol includes staged intravenous access versus HeRO graft placement, reverse Trendelenburg positioning, subcutaneous access of the deep portion of the existing catheter, use of a stiff wire placed within the inferior vena cava, dilation of the tract to 8 mm, device lubrication, all insertion procedures directly visualized, and use of immediate access conduits with SuperHeRO connector. Results: From 7/1/18 to 8/13/19, 55 HeRO grafts were placed at our institution following this protocol, average age 58 ± 15 (26–86) years (mean ± SD, range). 53 (96%) had had prior ipsilateral central access (13 by means of “inside out” 2 weeks prior) the other two had on-table access. Mean procedure time was 70 ± 26 (38–148) min. Excluding seven “complex” cases, procedure time for our first 20 cases using this protocol was 72 ± 29 min, while that of the last 28 was 62 ± 18 min ( p < 0.05). One patient suffered acute CHF after unclamping; despite reclamping and ligation he died on POD 3 (mortality rate 2%). 71% were done as outpatients, and 47 of 53 evaluable patients (89%) had their grafts used within 36 h for dialysis. Only one patient (2%) has had an infection within 30 days (cellulitis). At a mean followup of 95 ± 105 (maximum 383) days, three additional patients have had graft infections requiring excision, for a total infection rate of 5/53 (9%). Conclusions: Our results suggest that HeRO graft placement can be performed with minimal morbidity and mortality on an outpatient basis. Short-term infection rates are low and 89% of patients have their grafts immediately accessed and are discharged without a catheter.
CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event
Authors: Comabella Manuel , Clarke Margareta A , Schaedelin Sabine , Tintoré Mar , Pareto Deborah , Fissolo Nicolás , Pinteac Rucsanda , Granziera Cristina , Sastre-Garriga Jaume , Benkert Pascal , Auger Cristina , Kuhle Jens , Montalban Xavier , Rovira Alex 
Published: April 2021

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis. Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event. Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10–1.79; p < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47–3.60; p < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11–1.90; p < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses. Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.
Evaluation of temporal changes in the sexual function among Japanese women using the female sexual function index: An Internet survey
Authors: Okumura Keiko , Takeda Hirokazu , Otani Toshikazu 
Published: April 2021

Objectives: Female sexual dysfunction is an underestimated problem that negatively affects women’s quality of life. Although the overall prevalence of sexual dysfunction in women is high, only a few studies have focused on this problem. In Japan, an index of female sexual function has not been clearly defined. Hence, this study aimed to investigate the sexual function of normal Japanese women and the temporal changes they experienced using the Female Sexual Function Index administered online in 2012 and 2019. Methods: The subjects were Japanese women aged 20–79 years registered in an Internet research company. We collected data of 1034 and 2031 women in 2012 and 2019, respectively, based on Japan’s population distribution according to age. Subsequently, we analyzed the collected data using a Japanese version of the Female Sexual Function Index. We investigated the temporal changes in the Female Sexual Function Index total score, the ratio of women who did not engage in sexual activities and women having “no sexual activity” with their partners, and the total Female Sexual Function Index scores according to age. Results: The average Female Sexual Function Index total score decreased from 14.6 in 2012 to 12.5 in 2019 ( p < 0.001). No significant difference was observed in the average Female Sexual Function Index score of the group with sexual activity between 2012 (22.2) and 2019 (22.4). The ratio of women not engaging in sexual activities increased from 42.2% in 2012 to 54.0% in 2019. The ratio of women having “no sexual activity” with their partners increased by 10%. Conclusion: Comparison of data between 2012 and 2019 indicated that Japanese women have become less sexually active. The average Female Sexual Function Index total score of 22 may be useful as a reference value for diagnosing female sexual dysfunction in Japan.
Cytokine profiles and Lactobacillus species presence in pre-menopausal subjects with genital Mycoplasma genitalium or Ureaplasma urealyticum colonization
Authors: Garza John , Gandhi Kushal , Choi Sarah , Sanchez Asley , Ventolini Gary 
Published: April 2021

Background and Purpose: Lactobacilli play a vital role in protecting the vagina against pathogens. Cytokines are vital components of defense against infections in women. The genital mycoplasmas, Mycoplasma genitalium and Ureaplasma urealyticum, are associated with various infectious diseases in adults and infants. The objective of our study is to identify differences in cytokine profile and Lactobacillus species dominance between a study group of non-pregnant pre-menopausal women with genital M. genitalium or U. urealyticum colonization and a control group of non-pregnant pre-menopausal women without genital M. genitalium or U. urealyticum colonization. Methods: A real-time polymerase chain reaction was performed to measure Lactobacillus species in vaginal swab samples. Cytokine analysis was performed using multiplex immunoassay techniques. Analysis of variance confirmed a significant difference in cytokine profiles between patient groups, with t-tests identifying the most significantly different cytokines. Categorical data analysis identified significant patterns of relative Lactobacillus species dominance in the study group. Results: Lactobacillus iners was the predominant Lactobacillus species in the control group ( p = 0.005). There were no dominant Lactobacillus species observed in the study group. Vascular endothelial growth factor A ( p = 0.002), interleukin-8 ( p = 0.001), and interleukin-1β ( p = 0.049) were expressed significantly higher in the study group, whereas interleukin-1 receptor antagonist ( p < 0.001), interleukin-10 ( p = 0.001), interleukin-12 ( p = 0.002), and interferon-γ ( p = 0.022) were expressed higher in the control group. Association matrices for cytokines were significantly different between two groups ( p < 0.001), with mostly negative associations in the control group and mostly positive associations in the study group. Conclusion: Cytokine levels, their associations, and the patterns of Lactobacillus species dominance are observed to significantly diverge on the basis of M. genitalium and U. urealyticum colonization among non-pregnant pre-menopausal women.
Childhood intussusception: Correlation between ultrasound reports and intra-operative findings
Authors: Chukwubuike Kevin Emeka 
Published: April 2021

Background: Intussusception, a common cause of intestinal obstruction in children, is usually diagnosed through ultrasound scan. The aim of this study was to evaluate the correlation between the ultrasound report and intra-operating findings in children who had laparotomy for intussusception. Materials and methods: This was a retrospective study of children aged 12 months and below who had laparotomy for intussusception between January 2017–December 2019 at the pediatric surgery unit of Enugu State University Teaching Hospital Enugu, Nigeria. Findings at ultrasound and findings at surgery were statistically compared. Results: A total of 103 cases of intussusceptions were seen during the study period. Out of this number, 69 patients were treated by laparotomy and formed the basis of this report. There was male predominance and the median age of the patients was 8 months. Abdominal pain was the most common presenting symptom. At presentation, about one-quarter of the patients were anemic while one-half of the patients had electrolyte derangement. Comparing the findings at ultrasound and findings at surgery, ultrasound was found to have an accuracy of 89.9%. Approximately, equal number of patients had manual reduction and bowel resection. Surgical site infection was the most common post-operative complication and mortality occurred in 8 (11.6%) patients. Conclusion: Ultrasound has high accuracy rate and is quite reliable for the diagnosis of intussusception.
Petroselinum crispum, a commonly consumed food, affects sirolimus level in a renal transplant recipient: a case report
Authors: Kurtaran Melek , Koc Neriman Sila , Aksun Melek Seren , Yildirim Tolga , Yilmaz Şeref Rahmi , Erdem Yunus 
Published: April 2021

Sirolimus is an immunosuppressive drug used to prevent graft rejection. Therapeutic drug monitoring is required as with other immunosuppressive drugs. Previous studies have shown the interactions between sirolimus and drugs that affect the activity of cytochrome P450 3A4 and P-glycoprotein. There is an increasing tendency for the use of herbal remedies in many countries. Medicinal herbs are rich sources of natural bioactive compounds that could interact with drugs. Parsley, Petroselinum crispum, is a food, spice, and also a medicinal herb. We report a case of a renal transplant recipient who had a supratherapeutic blood level of sirolimus due to consuming excessive parsley to highlight a possible herb–drug interaction. This is the first case report describing sirolimus–parsley interaction. Herb–drug interactions are especially important for drugs with a narrow therapeutic window. For this reason, healthcare professionals should question all patients, especially transplant patients, about the use of herbs or herbal products and report interactions. Plain Language Summary Parsley, a commonly consumed food, affects the level of an important drug in a renal transplant recipient: A case report Sirolimus is a drug that suppresses the immune response used to prevent organ rejection in people who have had kidney transplants. In order to reach the optimum balance between therapeutic efficacy and adverse effects, sirolimus blood levels should be closely monitored. Previous studies have shown the interactions between sirolimus and drugs that affect the activities of metabolizing enzymes and transporter proteins. Parsley is a food, spice, and also a medicinal herb. Medicinal herbs are rich sources of natural bioactive compounds that could interact with a prescription drug. We report a case of a renal transplant recipient who had a rise in the blood level of sirolimus due to the ingestion of an excessive amount of parsley to highlight possible herb–drug interaction.
A survey of pediatric hematologists/oncologists’ perspectives on single patient Expanded Access and Right to Try
Authors: Chapman Carolyn Riley , Belli Hayley M , Leach Danielle , Shah Lesha D , Bateman-House Alison 
Published: April 2021

Introduction: Physicians in the United States play an essential role guiding patients through single patient pre-approval access (PAA) to investigational medical products via either the Food and Drug Administration (FDA)’s Expanded Access (EA) or the federal Right To Try (RTT) pathways. In this study, we sought to better understand pediatric hematologist/oncologists’ attitudes about seeking PAA, on behalf of single patients, to investigational drugs outside of clinical trials. Methods: A cross-sectional survey was developed and sent to pediatric hematologist/oncologists via St. Baldrick’s Foundation’s email distribution list. Results: Of 73 respondents (10.1% of those who received the survey), 56 met eligibility criteria and are included in the analysis. Over 80% ( n = 46) had prior experience with single patient PAA. Respondents were most concerned about the unknown risks and benefits of investigational drugs and financial implications of PAA for patients. One hundred percent and 91.1% of respondents indicated a willingness to support patients through EA and RTT pathways, respectively. When asked about their most recent experience with PAA, 40 out of 46 indicated that they used the FDA’s EA pathway to seek PAA and 4 out of 46 indicated that they used the RTT pathway. Of 44 respondents who had used the EA or RTT pathway, 43 indicated that the biotechnology or pharmaceutical company they solicited granted access to the requested product. Conclusion: Survey results support other findings suggesting a need for additional physician support and education about PAA and that physicians may have unequal access to information about investigational drugs and concerns about financial implications of PAA for their patients.
Evaluating predictors of renal injury with sorafenib in hepatocellular carcinoma: A multi-ethnic cohort study
Authors: Natsuhara Kelsey H , Zhang Li , Carlos Christopher A , Borno Hala T 
Published: April 2021

Background: Kidney injury is a well-described adverse event of tyrosine kinase inhibitors (TKIs), thought to be mediated predominantly through glomerular damage. However, risk factors for kidney injury and the mechanism of injury are poorly defined in a wide range of cancers. Methods: This is a secondary analysis of 539 patients in the control arm of an international randomized clinical trial of patients with hepatocellular carcinoma treated with sorafenib, a vascular endothelial growth-factor receptor (VEGFR) TKI. Risk factors for developing acute kidney injury (AKI) while being treated with sorafenib were evaluated by multivariable logistic regression. We performed subgroup analyses of AKI stratified into proteinuric and non-proteinuric AKI. Results: While on study, 16% of patients developed an AKI. A decrease in systolic blood pressure was positively associated with developing any AKI (OR 1.70, 95% CI 1.03–2.82). In the subgroup analyses, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI (OR 2.15, 95% CI 1.00–4.61), but there was no association with developing a non-proteinuric AKI. Conclusions: In patients with hepatocellular carcinoma taking sorafenib, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI. However, there was no association between a decrease in blood pressure and the development of a non-proteinuric AKI. Thus, the development of AKI among patients taking VEGFR-TKIs cannot be fully explained by a hemodynamic effect. Our study highlights the need to better understand the varying mechanisms of kidney injury in patients.
Tests for tuberculosis infection: landscape analysis
Authors: Hamada Yohhei , Cirillo Daniela Maria , Matteelli Alberto , Penn-Nicholson Adam , Rangaka Molebogeng X. , Ruhwald Morten 
Published: April 2021

BackgroundOnly the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube and T-SPOT.TB, are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than the TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed.MethodsWe reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally.ResultsWe identified 20 tests for TB infection: 15in vitrotests and five skin tests. 13 of thein vitrotests are whole-blood IGRAs and 14 use early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. 10 of the tests are based on assays other than an ELISA, such as a fluorescent lateral flow assay that requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared with the existing IGRAs. Four of the five skin tests use ESAT-6 and CFP-10 proteins, while the remaining test uses a new antigen that is specific toMycobacterium tuberculosiscomplex.ConclusionsNew tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.
Experimental Investigation on Micro Deep Drawing of Stainless Steel Foils with Different Microstructural Characteristics
Authors: Zhao Jingwei , Wang Tao , Jia Fanghui , Li Zhou , Zhou Cunlong , Huang Qingxue , Jiang Zhengyi 
Published: April 2021

AbstractIn the present work, austenitic stainless steel (ASS) 304 foils with a thickness of 50 µm were first annealed at temperatures ranging from 700 to 1100 ℃ for 1 h to obtain different microstructural characteristics. Then the effects of microstructural characteristics on the formability of ASS 304 foils and the quality of drawn cups using micro deep drawing (MDD) were studied, and the mechanism involved was discussed. The results show that the as-received ASS 304 foil has a poor formability and cannot be used to form a cup using MDD. Serious wrinkling problem occurs on the drawn cup, and the height profile distribution on the mouth and the symmetry of the drawn cup is quite non-uniform when the annealing temperature is 700 ℃. At annealing temperatures of 900 and 950 ℃, the drawn cups are both characterized with very few wrinkles, and the distribution of height profile, symmetry and mouth thickness are uniform on the mouths of the drawn cups. The wrinkling becomes increasingly significant with a further increase of annealing temperature from 950 to 1100 ℃. The optimal annealing temperatures obtained in this study are 900 and 950 ℃ for reducing the generation of wrinkling, and therefore improving the quality of drawn cups. With non-optimized microstructure, the distribution of the compressive stress in the circumferential direction of the drawn foils becomes inhomogeneous, which is thought to be the cause of the occurrence of localized deformation till wrinkling during MDD.
Capturing cognitive and behavioral variability among individuals with Down syndrome: a latent profile analysis
Authors:   The Down Syndrome Cognition Project, Channell Marie Moore , Mattie Laura J. , Hamilton Debra R. , Capone George T. , Mahone E. Mark , Sherman Stephanie L. , Rosser Tracie C. , Reeves Roger H. , Kalb Luther G. 
Published: April 2021

Abstract
Background
There is a high degree of inter- and intra-individual variability observed within the phenotype of Down syndrome. The Down Syndrome Cognition Project was formed to capture this variability by developing a large nationwide database of cognitive, behavioral, health, and genetic information on individuals with Down syndrome, ages 6–25 years. The current study used the Down Syndrome Cognition Project database to characterize cognitive and behavioral variability among individuals with Down syndrome.

Methods
Latent profile analysis was used to identify classes across a sample of 314 participants based on their cognition (IQ and executive functioning), adaptive and maladaptive behavior, and autism spectrum disorder symptomatology. A multivariate multinomial regression model simultaneously examined demographic correlates of class.

Results
Results supported a 3-class model. Each class demonstrated a unique profile across the subdomains of cognition and behavior. The “normative” class was the largest (n = 153, 48%) and displayed a relatively consistent profile of cognition and adaptive behavior, with low rates of maladaptive behavior and autism symptomatology. The “cognitive” class (n = 109, 35%) displayed low cognitive scores and adaptive behavior and more autism symptomatology, but with low rates of maladaptive behavior. The “behavioral” class, the smallest group (n = 52, 17%), demonstrated higher rates of maladaptive behavior and autism symptomatology, but with cognition levels similar to the “normative” class; their adaptive behavior scores fell in between the other two classes. Household income and sex were the only demographic variables to differ among classes.

Conclusions
These findings highlight the importance of subtyping the cognitive and behavioral phenotype among individuals with Down syndrome to identify more homogeneous classes for future intervention and etiologic studies. Results also demonstrate the feasibility of using latent profile analysis to distinguish subtypes in this population. Limitations and future directions are discussed.