bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Stapes-Head Coupler for the Vibrant Soundbridge System
Authors: Warnholtz Birthe , Schär Merlin , Cuny Pascale , Sonntag Kathrin , Beutner Dirk , Dobrev Ivo , Röösli Christof , Sim Jae Hoon
Published: March 2021

Introduction: The Vibrant Soundbridge (MED-EL Medical Electronics, Austria) is an active middle ear implant with a floating mass transducer (FMT) for patients with conductive, sensorineural, or mixed hearing loss. While the FMT is vertically aligned above the stapes head (SH) with the current Vibroplasty Clip coupler (MED-EL Medical Electronics), the new SH coupler was developed to mount the FMT on the inferior side of the stapes and to fit in the reduced middle ear space after canal-wall-down mastoidectomy. Methods: Using 11 human cadaveric temporal bones (TBs), placements of the new SH couplers on the stapes were examined, and effective stimuli to the cochlea were evaluated by measuring piston-like motion of the stapes footplate with a current of 1 mA on the FMT. The results were assessed in comparison with the Vibroplasty Clip coupler. Results: The new SH coupler showed perfect coupling on the stapes in 9 out of 11 TBs. A small gap between the SH and the plate of the connection link part was unavoidable in 2 TBs but had negligible effect on vibrational motion of the stapes. Vibrational motion of the stapes with the new SH coupler was reduced at frequencies above 3 kHz compared to the corresponding motion with the current Vibroplasty Clip coupler, but the relative attenuation over all 11 cadaveric temporal bones was <10 dB. Conclusions: The new SH coupler provides an alternative with more stable fixation when placement of the current Vibroplasty Clip coupler is limited due to insufficient space after canal-wall-down mastoidectomy, while still delivering effective stimuli to the cochlea.
A Multimethod Examination of Sensitivity to Reward and Sensitivity to Punishment in Bipolar Disorder and Alcohol Dependence: Results from a 2 × 2 Factorial Design
Authors: Mellick William , Prisciandaro James J. , Brenner Helena , Brown Delisa , Tolliver Bryan K.
Published: March 2021

Introduction: Shared neurobehavioral characteristics of bipolar disorder (BD) and alcohol dependence (AD), including heightened sensitivity to reward (SR), may account for high rates of BD and AD co-occurrence (BD + AD). However, empirical research is lacking. The present multimethod investigation examined SR and sensitivity to punishment (SP) among these patient groups using a reliable and well-validated self-report questionnaire of SR and SP along with a laboratory task specifically designed to distinguish SR and SP activation. Methods: One-hundred participants formed 4 groups: BD + AD (n = 40), BD (n = 18), AD (n = 25), and healthy controls (n = 17). Clinical interviews were administered, and participants completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSR-Q) and the Point Score Reaction Test behavioral task. Pearson correlations, hierarchical linear regression, and 2 × 2 factorial general linear modeling with Bonferroni-corrected pairwise comparisons were performed. Results: BD and AD main effects were significant on self-reported SR and SP; however, BD × AD interactions were not. BD + AD individuals were significantly higher on self-reported SR than BD and AD individuals, yet all clinical groups were similar on SP. Behavioral response times did not distinguish groups nor did they associate with self-report data. Discussion/Conclusion: BD and AD had additive, rather than interactive, effects on self-reported SR and SP. The methods employed, paired with their application to the present sample, may account for a lack of positive findings with behavioral data.
A Novel Artificial Urinary Sphincter (VICTO®) for the Management of Postprostatectomy Urinary Incontinence: Description of the Surgical Technique and Preliminary Results from a Multicenter Series
Authors: Giammò Alessandro , Falcone Marco , Blecher Gideon , Ammirati Enrico , Geretto Paolo , Manassero Alberto , Bottero Danilo , Lorusso Vito , Signorello Diego , Gontero Paolo , Carone Roberto
Published: March 2021

Aims: The objective of the study was to analyze short-term outcomes and safety profile of the newly designed artificial urinary sphincters (AUSs) VICTO® and VICTOplus®. Methods: Data from the implant of VICTO® or VICTOplus® AUSs on a series of consecutive male patients with stress urinary incontinence (SUI) following radical prostatectomy (RP) were retrospectively collected in 3 tertiary referral centers between May 2017 and December 2019. Patients were affected by moderate-severe genuine SUI (200–400 or >400 g urine leakage in 24-h pad test) refractory to conservative treatment. Outcomes were evaluated through the 24-h pad test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Follow-up was scheduled after 3, 6, and 12 months and then when clinically needed. Nonparametric tests were applied in subgroup analyses. Results: Seventeen patients were enrolled: 8 were implanted with the VICTO® device and 9 with VICTOplus®. The median age at surgery was 69 (interquartile range (IQR) 60–75) years. The median follow-up was 15 (IQR 12–18) months. At 12 months, the dry rate was 76.4% and the social continence rate was 94%. The postoperative complication rate was 17.6%. All complications were classified as Clavien-Dindo I. No difference in terms of outcomes was observed between the VICTO® and the VICTOplus® subgroups. Conclusions: Preliminary outcomes of the VICTO® and VICTOplus® implantation are satisfactory. These devices may represent a safe and realistic solution for patients with moderate-severe SUI following RP.
Analysis of Kytococcus sedentarius Strain Isolated from a Dehumidifier Operating in a University Lecture Theatre: Systems for Aerobic Respiration, Resisting Osmotic Stress, and Sensing Nitric Oxide
Authors: Alhadlaq Meshari Ahmed , Green Jeffrey , Kudhair Bassam K.
Published: March 2021

A strain of Kytococcus sedentarius was isolated from a dehumidifier operating in a university lecture theatre. Genome analysis and phenotypic characterisation showed that this strain, K. sedentarius MBB13, was a moderately halotolerant aerobe with a branched aerobic electron transport chain and genes that could contribute to erythromycin resistance. The major compatible solute was glycine betaine, with ectoine and proline being deployed at higher osmolarities. Actinobacteria possess multiple WhiB-like (Wbl) regulatory proteins, and K. sedentarius MBB13 has four (WhiB1, WhiB2, WhiB3, and WhiB7). Wbls are iron-sulfur proteins that regulate gene expression through interactions with RNA polymerase sigma factors and/or other regulatory proteins. Bacterial two-hybrid analyses suggested that WhiB1 and WhiB2, but not WhiB3 and WhiB7, interact with the C-terminal domain of the major sigma factor, σA; no interaction was detected between any of the Wbl proteins and the only alternative sigma factors, σB, σH, or σJ. The interaction between σA and WhiB1 or WhiB2 was disrupted in a heterologous system under growth conditions that produce nitric oxide and the iron-sulfur clusters of the isolated WhiB1 and WhiB2 proteins reacted with nitric oxide. Thus, K. sedentarius strain exhibits the major phenotypic characteristics of the type strain and a comprehensive examination of the interactions between its four Wbl proteins and four sigma factors suggested that the Wbl proteins all operate through interaction with σA.
Differences between Pressurized and Non-Pressurized Transient-Evoked Otoacoustic Emissions in Neonatal Subjects
Authors: Zimatore Giovanna , Skarzynski Piotr Henryk , Di Berardino Federica , Filipponi Eliana , Hatzopoulos Stavros
Published: March 2021

Introduction: Recently, Interacoustics presented a new otoacoustic emission protocol where the probe pressurizes the ear cavity, thus eliminates the risk of non-assessment (REFER outcome) due to a negative middle ear pressure. This study evaluated the characteristics and the performance of this new protocol on a newborn well-baby population. Methods: One hundred sixty-three newborns (age 2.7 ± 1.1 days) for a total of 294 ears were assessed randomly. Transiently evoked otoacoustic responses were acquired by the Titan device (Interacoustics), using the default and a pressurized TEOAE protocol. The data were analyzed in terms of signal to noise ratios (S/Ns) at 5 frequencies, namely, 0.87, 1.94, 2.96, 3.97, and 4.97 kHz. To assess any possible gestational age (GE) effects on the TEOAE variables, the responses were subdivided in 4 different age subgroups. Results: There were no significant differences between the left and right ear TEOAE responses, for age (in days), GE (in weeks), weight (in grams), and S/N at all 5 frequencies. Considering the pooled 294 ears, paired t tests between the default and the pressurized TEOAE data showed significant differences across all 5 frequencies (p < 0.01). The pressurized protocol generated TEOAE responses presenting larger S/Ns, and a positive additive effect of approximately 2.31 dB was observed at all tested frequencies. There were no significant GE effects on the pressurized TEOAE responses. In terms of performance, both protocols performed equally (same number of PASSes). Conclusion: The pressurized TEOAE protocol generates responses with higher S/Ns which might be useful in borderline cases where the middle ear status might cause a REFER screening outcome.
Atypical Clinical Presentation of Persistent Müllerian Duct Syndrome in Siblings
Authors: Globa Evgenia , Zelinska Nataliya , Siryk Nina , Bashamboo Anu , McElreavey Kenneth
Published: March 2021

Persistent Müllerian duct syndrome (PMDS) is a rare autosomal recessive disorder characterized by the lack of regression of the derivatives of the Müllerian ducts in males. Boys with this condition usually present with unilateral or bilateral cryptorchidism, inguinal hernias, and reproductive disorders with normal male genitalia. Variants in the AMH or AMHR2 genes are responsible for the development of this syndrome. The genetic diagnosis and surgery in PMDS is challenging for both the endocrinologist and the urologist. Here, we describe the management of 2 siblings from 1 family who presented with bilateral cryptorchidism and hypospadias at birth. One child had testis located in the pelvis in the position of normal ovaries, while the other child had testis which were located in the inguinal canals (bilateral inguinal cryptorchidism). Exome sequencing revealed a compound heterozygous variant in the AMHR2 gene c.1388G>A, p.R463H and c.1412G>A p.R471H. To our knowledge, hypospadias has not been described in association with PMDS.
Screening Status as a Determinant of Choice of Colorectal Cancer Screening Method: A Population-Based Informed Survey
Authors: Sandoval José Luis , Relecom Allan , Ducros Cyril , Bulliard Jean-Luc , Arzel Beatrice , Guessous Idris
Published: March 2021

Objectives: Fecal blood testing is a noninvasive alternative to colonoscopy for colorectal cancer (CRC) screening and is preferred by a substantial proportion of individuals. However, participant-related determinants of the choice of screening method, particularly up-to-date screening status, remain less studied. We aimed to determine if up-to-date screening status was related to choosing a fecal blood test over colonoscopy. Setting: Participants in the population-based cross-sectional survey study Bus Santé in Geneva, Switzerland – aged 50–69 years. Design: Cross-sectional survey study using mailed questionnaires inquiring about CRC screening method of choice after providing information on advantages and disadvantages of both screening methods. We used multivariable logistic regression models to determine the association between up-to-date CRC screening status and choosing fecal blood testing. Key results: We included 1,227 participants. Thirty-eight percent of participants did not have up-to-date CRC screening. Overall, colonoscopy (54.9%) was preferred to fecal blood testing (45.1%) (p < 0.001) as screening method of choice. However, screening method choices differed between those with (65.6% colonoscopy and 34.4% fecal blood testing) and without up-to-date CRC screening (36.5% colonoscopy and 63.5% fecal blood testing). Not having up-to-date CRC screening was associated with a higher probability of choosing fecal blood testing as screening method (odds ratio = 2.6 [1.9; 3.7], p < 0.001) after adjustment for the aforementioned confounders. Conclusions: Not having up-to-date screening was independently associated with fecal blood testing as the preferred method for CRC screening. Proposing this method to this subpopulation, in a context of shared decision, could potentially increase screening uptake in settings where it is already high.
Hypoxia Reduces the Transcription of Fibrotic Markers in the Intestinal Mucosa
Authors: Simmen Simona , Maane Max , Rogler Sarah , Baebler Katherina , Lang Silvia , Cosin-Roger Jesus , Atrott Kirstin , Frey-Wagner Isabelle , Spielmann Partick , Wenger Roland H. , Weder Bruce , Zeitz Jonas , Vavricka Stephan R. , Rogler Gerhard , de Vallière Cheryl , Hausmann Martin , Ruiz Pedro A.
Published: March 2021

Introduction: Intestinal fibrosis, characterized by excessive deposition of extracellular matrix proteins, is a common and severe clinical complication of inflammatory bowel disease (IBD). However, the mechanisms underlying fibrosis remain elusive, and currently, there are limited effective pharmacologic treatments that target the development of fibrosis. Hypoxia is one of the key microenvironmental factors influencing intestinal inflammation and has been linked to fibrosis. Objective: In the present study, we sought to elucidate the impact of hypoxia on fibrotic gene expression in the intestinal mucosa. Methods: Human volunteers, IBD patients, and dextran sulphate sodium-treated mice were exposed to hypoxia, and colonic biopsies were collected. The human intestinal epithelial cell line Caco-2, human THP-1 macrophages, and primary human gut fibroblasts were subjected to hypoxia, and changes in fibrotic gene expression were assessed. Results: Human volunteers subjected to hypoxia presented reduced transcriptional levels of fibrotic and epithelial-mesenchymal transition markers in the intestinal mucosa. IBD patients showed a trend towards a decrease in tissue inhibitor of metalloproteinase 1 protein expression. In mice, hypoxic conditions reduced the colonic expression of several collagens and matrix metalloproteinases. Hypoxic Caco-2 cells, THP-1 cells, and primary gut fibroblasts showed a significant downregulation in the expression of fibrotic and tissue remodelling factors. Conclusions: Stabilization of hypoxia-inducible factors might represent a novel therapeutic approach for the treatment of IBD-associated fibrosis.
Effectiveness and Distribution of Testosterone Levels within First Year of Androgen Deprivation Therapy in a Real-World Setting: Results from the Non-Interventional German Cohort LEAN Study
Authors: Schmitz-Dräger Bernd J. , Mühlich Stephan , Lange Carsten , Benderska-Söder Natalya , Bismarck Ekkehardt , Starlinger Roland , Ottillinger Bertram , Hakenberg Oliver W.
Published: March 2021

Background: Observational studies generate information on real-world therapy and complement data from prospective randomized trials. LEAN is an open-label, non-interventional, multi-centre, German cohort study on leuprorelin in routine clinical practice. Objectives: To extend knowledge on the use, effectiveness, and tolerability of HEXAL/Sandoz leuprorelin (in this article, the term Leuprone® HEXAL® covers Leuprorelin Sandoz® as well) solid implant in patients with prostate cancer (PCa) in a real-world setting. Methods: 959 PCa patients scheduled for androgen deprivation therapy (ADT) received leuprorelin acetate implant. Metabolism, serum prostate-specific antigen (PSA), and testosterone data, if available, were collected at baseline and follow-up visits for ≥12 months. Results: Of 694 patients in the modified full analysis set, 26.4% received GnRH analogues ≤6 months before enrolment. Fifty-one percent of patients were treated for locally advanced or metastatic PCa. In 19.6% of patients, ADT was used in neoadjuvant or adjuvant settings and in 28.5% with rising PSA after definite therapy. Testosterone levels <0.5 ng/mL were achieved in >90% of patients. Safety profile was in line with the summary of product characteristics. Therapy was well tolerated, with patient-triggered therapy discontinuation in 3.6%. Conclusions: This interim analysis confirmed previous efficacy findings for leuprorelin implant in a real-world setting. This contemporary cohort showed a shift in the use of ADT to non-metastatic PCa stages.
Nocturnal Traction: Techniques Used for Hair Style Maintenance while Sleeping May Be a Risk Factor for Traction Alopecia
Authors: Samrao Aman , McMichael Amy , Mirmirani Paradi
Published: March 2021

Background: Traction alopecia (TA) is a preventable form of hair loss that most commonly affects women. It is the result of chronic use of hairstyles that put tension on hair. Public health efforts to increase awareness of this condition are critical. Early recognition by health care providers, along with counseling and cessation of offending hair care practices can impact severity of hair loss. Objectives: In a patient with patchy hair loss, having a high index of suspicion for TA and looking for clues in the history and exam, can help establish an accurate diagnosis. Methods: Patients with afro-textured or curly hair may use various techniques to maintain their hairstyles while sleeping in order to avoid time-consuming and/or expensive hair care. This behavior is not commonly recognized or addressed. Results and Conclusions: Increased awareness of “nocturnal traction” and asking patients “How do you wear your hair when you sleep?” may help identify at-risk patients.
Composition of Urine Collected from Non-Stone-Forming Chinese Persons during Different Short-Term Periods of the Day
Authors: He Zhican , Chang Zhenglin , An Lingyue , Lei Min , Jiang Zheng , Ou Lili , Wu Wenqi , Tiselius Hans-Göran
Published: March 2021

The purpose of this study in a small group of non-stone-forming Chinese persons was to measure the levels of supersaturation with calcium oxalate and calcium phosphate and pH with the aim of confirming if any of the different short-term urine samples were better for risk evaluation than a 24-h sample. Nine normal men and 1 woman collected urine during 4 periods of the day. Period 1 between 08 and 12 h, Period 2 between 12 and 18 h, Period 3 between 18 and 22 h, and Period 4 between 22 and 08 h. Each sample was analysed for calcium, oxalate, citrate, magnesium and phosphate, and estimates of supersaturation with calcium oxalate (CaOx) and calcium phosphate (CaP) were expressed in terms of AP(CaOx) and AP(CaP) index. An estimate of the solute load of CaOx was also calculated. Urine composition for 24-h urine (Period 24) was obtained mathematically from the analysed variables. Urine composition corresponding to 14-h urine portions 22–12 h (Period 14N) and 08–22 h (Period 14 D) were calculated. The lowest pH levels were recorded in Period 1 urine. The highest level of AP(CaOx) index was recorded during Period 1, and the product AP(CaOx) index × 107 × hydrogen ion concentration was significantly higher in Period 1 urine than in 24-h urine (p = 0.02). Also, the product SL(CaOx) × 107 × hydrogen ion concentration was significantly higher in Period 1 urine (p = 0.02). Low AP (CaP) index levels were recorded in Period 4, but also in all periods following dietary loads of calcium and phosphate. With the important reservation that the analytical results were obtained from non-stone-forming persons, the conclusion is that analysis of urine samples collected between 08 and 12 h might be an alternative to 24-h urine. The risk evaluation might advantageously be expressed either in terms of the product AP(CaOx) index × 107 × hydrogen ion concentration or the product SL(CaOx) × 107 × hydrogen ion concentration.
Potential Pitfalls in Pre-implantation Genetic Diagnosis in a Patient with Tuberous Sclerosis and Isolated Mosaicism for a TSC2 Variant in Renal Tissue
Authors: Ikeda Kristin M. , House Andrew A. , Connaughton Dervla M. , Pautler Stephen E. , Siu Victoria Mok , Jones Michelle-Lee
Published: March 2021

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that displays a wide spectrum of clinical manifestations, often affecting multiple organs including the kidneys, brain, lungs, and skin. A pathogenic mutation in either the TSC1 or TSC2 gene can be detected in almost 85% of the cases, with mosaicism accounting for about half of the remaining cases. We report a case of TSC diagnosed clinically, requesting genetic counselling regarding reproductive risks. No mutation was identified on initial testing of peripheral blood; however, mosaicism for a likely pathogenic frameshift variant in TSC2 was detected at a level of 15% in renal angiomyolipoma tissue. Despite widespread clinical manifestations of TCS, this variant was not detected in skin fibroblasts or saliva, raising the possibility this is an isolated somatic mutation in renal tissue with the underlying germline mutation not yet identified. This case highlights the difficulties when counselling patients with mosaicism regarding their reproductive risks and prenatal diagnostic options.
Early Crypt Formation Defects in the Uterine Epithelia of Sox17 Heterozygous Mice
Authors: Hirate Yoshikazu , Hayakawa Kana , Nakano Yuki , Kumazawa Shiori , Miura Kento , Kanai Yoshiakira , Kanai-Azuma Masami
Published: March 2021

SOX17 activity in the uterine epithelium is essential for the implantation of mouse embryos. Previously, we demonstrated that female Sox17 heterozygous mutant mice are subfertile, and 2 active copies of Sox17 are required for the proper implantation of mouse embryos. To understand which implantation step is most sensitive to the Sox17 gene dosage, we comprehensively investigated the phenotypes and RNA transcriptomes of Sox17 heterozygous mutant mice. Uterine Sox17 expression drastically changed according to estrous cycle and during early pregnancy. The highest Sox17 expression was observed during the receptive period for blastocyst implantation. Sox17 heterozygous uterine epithelia showed ectopic high-level expression of SOX9, another SOX factor that is normally expressed in the uterine gland. Three-dimensional analysis of the uterus on day 5 of pregnancy revealed no crypt formation near the healthy blastocysts in the Sox17 heterozygous uterine epithelium, suggesting that early defects in embryo homing had occurred. Global transcriptional analysis revealed that the expression of Amphiregulin (Areg), a gene encoding a heparin-binding epidermal growth factor receptor ligand, was decreased drastically in Sox17+/− uterine epithelia. These data imply that full Sox17 activity is required to promote early crypt formation through proper regulation of SOX9 and AREG expression at the implantation site.
Pure Distal 7q Duplication: Describing a Macrocephalic Neurodevelopmental Syndrome, Case Report and Review of the Literature
Authors: Bosfield Kerri , Diaz Jullianne , Leon Eyby
Published: March 2021

Pure distal duplications of 7q have rarely been described in the medical literature. The term pure refers to duplications that occur without an accompanying clinically significant deletion. Pure 7q duplications of various segments have previously been reported in the literature; however, pure distal 7q duplications have only been reported in 21 cases. Twenty of these earlier reports described patients who were identified via karyotype and 1 recently by microarray. Cases have also been reported in genomic databases such as DECIPHER and the University of California Santa Cruz genome browser. We have reviewed 7 additional cases with distal 7q duplications from these databases and compared them to 7 previously reported distal 7q duplication cases to uncover common features including global developmental delay, frontal bossing, macrocephaly, seizures, kyphoscoliosis/skeletal anomalies, and microretrognathia/palatal anomalies. In this case, we describe a 4-year-old boy with a 30.8-Mb pure duplication of 7q32.1q36.3. Newly reported features associated with this duplication include intermittent dystonic posturing, increased behavioral irritability, eosinophilic esophagitis, segmental vertebral anomalies, and segmental intermittent limb cyanosis. We highlight the importance of using publicly available databases to describe rare genetic syndromes and to better characterize the features of pure distal 7q duplications and further postulate that duplication of this region represents a recognizable macrocephalic neurodevelopmental syndrome.
Combination of Robotic Pyeloplasty and Percutaneous Renal Surgery for Simultaneous Treatment of Ureteropelvic Junction Obstruction and Calyx Stones
Authors: Hüttenbrink Clemens , Kelm Peter , Klein Tilman , Distler Florian , Pandey Abishek , Pahernik Sascha
Published: March 2021

Introduction: Ureteropelvic junction obstruction (UPJO) and the simultaneous presence of kidney calyx stones represent a challenge for renal surgery. We present a novel technique for the simultaneous treatment of UPJO by robotic pyeloplasty in combination with the percutaneous endoscopic treatment of kidney calyx stones by flexible nephroscopy. Patients and Methods: Between January 2018 and February 2020, 4 patients were diagnosed with UPJO and simultaneous pelvic or calyceal stones. UPJO was treated by conventional robotic pyeloplasty. After opening the renal pelvis, a flexible 16-French cystoscope was introduced via the 12-mm assistant trocar into the renal pelvis. The kidney calyx stones (n = 1–15) were removed endoscopically through a flexible nephroscope using a Dormia helical basket. Before suturing the anastomosis of the renal pelvis, a ureter stent was inserted. Results: After the procedure, all patients were stone free. Using the Clavien-Dindo classification, no complications were noted. The mean size of the calculi was 6.69 mm (range: 1–25). Up to 15 calyx stones (mean 3.46) were removed per patient. A complete stone clearance confirmed by postoperative X-ray imaging was achieved in all patients. The mean operative time was 149 min (range: 130–178). Mean hospital stay was 7 days (7–8). The urethral stent was removed after 4–6 weeks. Conclusions: Robotic management of UPJO and simultaneous flexible nephroscopy for removal of calyceal stones is an effective treatment in 1 session. Combining robotic surgery with flexible percutaneous renal surgery is a feasible, safe, and effective method of the treatment of UPJO and concomitant calyceal stones.
Reward-Related Attentional Capture Moderates the Association between Fear-Driven Motives and Heavy Drinking
Authors: Liu Chang , Yücel Murat , Suo Chao , Le Pelley Mike E. , Tiego Jeggan , Rotaru Kristian , Fontenelle Leonardo F. , Albertella Lucy
Published: March 2021

Background: To date, there has been little investigation on how motivational and cognitive mechanisms interact to influence problematic drinking behaviours. Towards this aim, the current study examined whether reward-related attentional capture is associated with reward, fear (relief), and habit drinking motives, and further, whether it interacts with these motives in relation to problematic drinking patterns. Methods: Ninety participants (mean age = 34.8 years, SD = 9.1, 54% male) who reported having consumed alcohol in the past month completed an online visual search task that measured reward-related attentional capture as well as the Habit Reward Fear Scale, a measure of drinking motives. Participants also completed measures of psychological distress, impulsivity, compulsive drinking, and consumption items of Alcohol Use Disorders Identification Test. Regression analyses examined the associations between motives for alcohol consumption and reward-related attentional capture, as well as the associations between reward-related attentional capture, motives, and their interaction, with alcohol consumption and problems. Results: Greater reward-related attentional capture was associated with greater reward motives. Further, reward-related attentional capture also interacted with fear motives in relation to alcohol consumption. Follow-up analyses showed that this interaction was driven by greater fear motives being associated with heavier drinking among those with lower reward-related attentional capture (i.e., “goal-trackers”). Conclusion: These findings have implications for understanding how cognition may interact with motives in association with problematic drinking. Specifically, the findings highlight different potential pathways to problematic drinking according to an individual’s cognitive-motivational profile and may inform tailored interventions to target profile-specific mechanisms. Finally, these findings offer support for contemporary models of addiction that view excessive goal-directed behaviour under negative affect as a critical contributor to addictive behaviours.
A Retrospective Cohort Study Comparing In-Person and Telemedicine-Based Opioid Agonist Treatment in Ontario, Canada, Using Administrative Health Data
Authors: Morin Kristen A. , Parrotta Matthiew D. , Eibl Joseph K. , Marsh David C.
Published: March 2021

Background: This study evaluated how telemedicine as a modality for opioid agonist treatment compares to in-person care. Methods: We conducted a retrospective cohort study of patients enrolled in opioid agonist treatment between January 1, 2011, and December 31, 2015, in Ontario, Canada. We compared patients who received opioid agonist treatment predominantly in person, mixed, and predominantly by telemedicine. We used a logistic regression model to evaluate mortality, a Cox proportional hazard model to assess retention, and a negative binomial regression model to evaluate emergency department visits and hospitalizations. The study was performed using administrative health data with physician billing data from the Ontario Health Insurance Plan and prescription data from the Ontario Drug Benefit databases. Results: A total of 55,924 individuals were included in the study. Receiving opioid agonist treatment by predominantly telemedicine was not associated with all-cause mortality (OR = 0.9, 95% CI: 0.8–1.0), 1-year treatment retention (OR = 1.0, 95% CI: 0.9–1.1), or opioid-related emergency department visits and hospitalizations when compared to in-person care. The rate of emergency department visits (IRR = 1.4), the rate of mental health-related emergency department visits (IRR = 1.5), and the rate of mental health-related hospitalizations per year (IRR = 1.2) was higher for patients who received opioid agonist treatment predominantly by telemedicine compared to in person. Conclusion: Our findings support the conclusion that telemedicine is equal to in-person care regarding mortality opioid-related emergency department visits and retention, and is a viable option for those seeking opioid agonist treatment.
Homozygous Missense Variation in PNPLA8 Causes Prenatal-Onset Severe Neurodegeneration
Authors: Masih Suzena , Moirangthem Amita , Phadke Shubha R.
Published: March 2021

The patatin-like protein family plays an important role in various biological functions including lipid homeostasis, cellular growth, and signaling. Conserved across species, the patatin domain is shared by all 9 members of the PNPLA family without redundancy in the coding sequences. The defective function of PNPLA2, PNPLA6, and PNPLA9 are known to cause mitochondrial-related neurodegeneration. Recently, PNPLA8 has been associated with mitochondrial myopathy and poor weight gain with lactic acidosis in 3 unrelated families. Using whole-exome sequencing, we identified a homozygous novel missense variation c.1874A>G in the patatin domain of PNPLA8. The patient had prenatal-onset severe and progressive neurodegeneration with mortality in infancy.
Maternal and Fetal Outcomes in Women with Brain Arteriovenous Malformation Rupture during Pregnancy
Authors: Yan Kimberly L. , Ko Nerissa U. , Hetts Steven W. , Weinsheimer Shantel , Abla Adib A. , Lawton Michael T. , Kim Helen
Published: March 2021

Background: Sporadic brain arteriovenous malformations (BAVM) are a major cause of hemorrhagic stroke in younger persons. Prior studies have reported contradictory results regarding the risk of hemorrhage during pregnancy, and there are no standard guidelines for the management of pregnant women who present with BAVM rupture. The purpose of this study is to describe maternal and fetal outcomes and treatment strategies in patients with BAVM hemorrhage during pregnancy. Methods: We performed a retrospective review of the University of California, San Francisco Brain AVM Project database for female patients who were pregnant at the time of BAVM hemorrhage between 2000 and 2017. Clinical and angiographic characteristics at presentation, BAVM treatment, and maternal outcomes using modified Rankin scale (mRS) score at presentation and 2-year follow-up were recorded. Fetal outcomes were abstracted from medical records and maternal reports. Results: Sixteen patients presented with BAVM hemorrhage during pregnancy, 81% (n = 13) of whom were in their second or third trimester. Three patients (19%) who were in their first trimester terminated or miscarried pregnancy prior to BAVM intervention. Of the remaining 13 patients, 77% (n = 10) received emergent BAVM treatment at time of hemorrhage prior to delivery, and 85% of patients achieved BAVM obliteration and good maternal outcomes (mRS 0–2) at 2-year follow-up. All patients had uncomplicated deliveries (69% cesarean and 23% vaginal) with no reports of postnatal cognitive or developmental delays in infants at 2-year follow-up. Conclusions: Our study shows good long-term maternal and fetal outcomes in ruptured BAVM patients presenting during pregnancy, the majority who received BAVM interventional treatment prior to delivery.
Positive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells
Authors: Wang Yi , Huo Zhiting , Lin Quanshi , Lin Yuxia , Chen Cancan , Huang Yanxia , Huang Changbai , Zhang Junsong , He Junfang , Liu Chao , Zhang Ping
Published: March 2021

Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.
The Rationale and Evidence for SGLT2 Inhibitors as a Treatment for Nondiabetic Glomerular Disease
Authors: Miyata Kana N. , Zhang Shao-Ling , Chan John S.D.
Published: March 2021

Background: Recent studies show that sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally approved for glycemic control in patients with type 2 diabetes, also exert renoprotective effects independently from effects on dysglycemia. Moreover, recent work indicates that SGLT2i treatment may be effective in patients with nondiabetic chronic kidney disease, including primary and secondary glomerular diseases. Summary: SGLT2i lower blood glucose by blocking glucose resorption in the early renal proximal tubule through the glucose transporter, SGLT2, leading to enhanced urinary glucose excretion. Recent studies indicate that SGLT2i may have pleiotropic effects on cells other than proximal tubular cells. SGLT2i reduce the glomerular workload by decreasing the intraglomerular pressure, thus ameliorating hyperfiltration, if present, and may also decrease systemic blood pressure. SGLT2i may also act directly on endothelial cells, possibly via modulating the effects of adhesion molecules and reducing inflammatory cytokines and reactive oxygen species. SGLT2i may have direct anti-inflammatory and antifibrotic effects on renal tubules. Some reports suggest direct protective effects on podocytes and mesangial cells as well. Here, we provide a review of the potential mechanisms of renoprotection, therapeutic utility, and potential side effects of SGLT2i in patients with nondiabetic glomerular diseases, based on data from studies carried out in cells, experimental animals, and humans. Key Messages: SGLT2i may be a promising addition to the glomerular disease treatment armamentarium. However, it is unclear at what point of the natural history of specific glomerular diseases (whether this is immune or nonimmune mediated) SGLT2i can be beneficial. Additionally, further studies are needed to assess the long-term efficacy and safety of SGLT2i in patients with nondiabetic glomerular diseases.
Deoxycytidine Kinase (DCK) Mutations in Human Acute Myeloid Leukemia Resistant to Cytarabine
Authors: Wu Biao , Mao Zhengwei Jenny , Wang Zhi , Wu Pin , Huang Hongyu , Zhao Wenjun , Zhang Lei , Zhang Zhou , Yin Hongchao , Gale Robert Peter , Yin Bin
Published: March 2021

Resistance to cytarabine is an important cause of therapy failure in persons with acute myeloid leukemia (AML). Deoxycytidine kinase, encoded by DCK, catalyzes phosphorylation of cytarabine to cytarabine monophosphate, a necessary step for eventual incorporation of cytarabine triphosphate into DNA and for clinical efficacy. Whether DCK mutations make AML cells resistant to cytarabine is controversial. We studied DCK mutations and messenger RNA (mRNA) concentrations in leukemia cells from 10 subjects with AML who received cytarabine-based therapy and relapsed and in 2 artificially induced cytarabine-resistant AML cell lines. DCK mutations were detected in 4 subjects with AML relapsing after achieving a complete remission and receiving high-dose cytarabine postremission therapy. Most mutations were in exons 4–6 and were not present before therapy. DCK was also mutated in cytarabine-resistant but not parental AML cell lines. DCK mRNA concentrations were significantly decreased in cytarabine-resistant K562 and SHI-1 cells compared with cytarabine-sensitive parental cells. Mutation frequency of DCK and mRNA concentration did not correlate with the extent of cytarabine resistance indicating other factors operate. Overexpression of wild-type DCK restored cytarabine sensitivity to previously resistant leukemia cell lines. Our data contribute to the understanding of cytarabine resistance in persons with AML.
Comparison of Approaches for Prediction of Renal Replacement Therapy-Free Survival in Patients with Acute Kidney Injury
Authors: Pattharanitima Pattharawin , Vaid Akhil , Jaladanki Suraj K. , Paranjpe Ishan , O’Hagan Ross , Chauhan Kinsuk , Van Vleck Tielman T. , Duffy Aine , Chaudhary Kumardeep , Glicksberg Benjamin S. , Neyra Javier A. , Coca Steven G. , Chan Lili , Nadkarni Girish N.
Published: March 2021

Background/Aims: Acute kidney injury (AKI) in critically ill patients is common, and continuous renal replacement therapy (CRRT) is a preferred mode of renal replacement therapy (RRT) in hemodynamically unstable patients. Prediction of clinical outcomes in patients on CRRT is challenging. We utilized several approaches to predict RRT-free survival (RRTFS) in critically ill patients with AKI requiring CRRT. Methods: We used the Medical Information Mart for Intensive Care (MIMIC-III) database to identify patients ≥18 years old with AKI on CRRT, after excluding patients who had ESRD on chronic dialysis, and kidney transplantation. We defined RRTFS as patients who were discharged alive and did not require RRT ≥7 days prior to hospital discharge. We utilized all available biomedical data up to CRRT initiation. We evaluated 7 approaches, including logistic regression (LR), random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), multilayer perceptron (MLP), and MLP with long short-term memory (MLP + LSTM). We evaluated model performance by using area under the receiver operating characteristic (AUROC) curves. Results: Out of 684 patients with AKI on CRRT, 205 (30%) patients had RRTFS. The median age of patients was 63 years and their median Simplified Acute Physiology Score (SAPS) II was 67 (interquartile range 52–84). The MLP + LSTM showed the highest AUROC (95% CI) of 0.70 (0.67–0.73), followed by MLP 0.59 (0.54–0.64), LR 0.57 (0.52–0.62), SVM 0.51 (0.46–0.56), AdaBoost 0.51 (0.46–0.55), RF 0.44 (0.39–0.48), and XGBoost 0.43 (CI 0.38–0.47). Conclusions: A MLP + LSTM model outperformed other approaches for predicting RRTFS. Performance could be further improved by incorporating other data types.
Validation of an Algorithm to Detect Multiple Sclerosis Cases in Administrative Health Databases in Piedmont (Italy): An Application to the Estimate of Prevalence by Age and Urbanization Level
Authors: Gnavi Roberto , Picariello Roberta , Alboini Paolo Emilio , Cavalla Paola , Grasso Maria Federica , Richiardi Paola , Bertolotto Antonio , Barizzone Nadia , Cantello Roberto , Leone Maurizio Angelo , D’Alfonso Sandra , Golini Natalia
Published: March 2021

Introduction: Italy is considered a high-risk country for multiple sclerosis (MS). Exploiting electronic health archives (EHAs) is highly useful to continuously monitoring the prevalence of the disease, as well as the care delivered to patients and its outcomes. The aim of this study was to validate an EHA-based algorithm to identify MS patients, suitable for epidemiological purposes, and to estimate MS prevalence in Piedmont (North Italy). Methods: MS cases were identified, in the period between January 1, 2012 and December 31, 2017, linking data from 4 different sources: hospital discharges, drug prescriptions, exemptions from co-payment to health care, and long-term care facilities. Sensitivity of the algorithm was tested through record linkage with a cohort of 656 neurologist-confirmed MS cases; specificity was tested with a cohort of 2,966,293 residents presumably not affected by MS. Undercount was estimated by a capture-recapture method. We calculated crude, and age- and gender-specific prevalence. We also calculated age-adjusted prevalence by level of urbanization of the municipality of residence. Results: On December 31, 2017, the algorithm identified 8,850 MS cases. Sensitivity was 95.9%, specificity was 99.97%, and the estimated completeness of ascertainment was 91.9%. The overall prevalence, adjusted for undercount, was 152 per 100,000 among men and 286 among women; it increased with increasing age and reached its peak value in the 45- to 54-year class, followed by a progressive reduction. The age-adjusted prevalence of residents in cities was 15% higher than in those living in the countryside. Discussion/Conclusion: We validated an algorithm based on EHAs to identify cases of MS for epidemiological use. The prevalence of MS, adjusted for undercount, was among the highest in Italy. We also found that the prevalence was higher in highly urbanized areas.
A Review of Nail Changes in Acrokeratosis Paraneoplastica (Bazex Syndrome)
Authors: Roy Bipasha , Lipner Shari R.
Published: March 2021

Acrokeratosis paraneoplastica (Bazex syndrome) is a rare paraneoplastic dermatosis associated with internal malignancies. Clinical presentation is characterized by erythematous or violaceous scaly plaques involving the digits, nose, ears, palms, and soles. Nail changes commonly present concurrently with cutaneous manifestations. In this review, we characterize nail changes associated with acrokeratosis paraneoplastica. A total of 48 cases were analyzed. Nail findings were nonspecific, with the most common being nail plate thickening, onycholysis, subungual hyperkeratosis, longitudinal ridging, discoloration, and nail plate loss. In most patients, nail changes involved the majority of fingernails and toenails and most often appeared prior to the diagnosis of malignancy. The most common associated underlying malignancies were squamous cell carcinomas of the head and neck. A diagnosis of acrokeratosis paraneoplastica should be considered in patients with onychodystrophy involving multiple nails with accompanying atypical psoriasiform dermatoses. Screening for internal malignancies may significantly decrease morbidity and mortality for these patients.
Living Well with Kidney Disease by Patient and Care-Partner Empowerment: Kidney Health for Everyone Everywhere
Authors: Kalantar-Zadeh Kamyar , Li Philip Kam-Tao , Tantisattamo Ekamol , Kumaraswami Latha , Liakopoulos Vassilios , Lui Siu-Fai , Ulasi Ifeoma , Andreoli Sharon , Balducci Alessandro , Dupuis Sophie , Harris Tess , Hradsky Anne , Knight Richard , Kumar Sajay , Ng Maggie , Poidevin Alice , Saadi Gamal , Tong Allison ,   for the World Kidney Day Steering Committee
Published: March 2021

Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD-related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of “Living Well with Kidney Disease” in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labelling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities, including during pandemics. In the overall wellness program for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policy makers, applicable to both developed and developing countries.