bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evaluation of [68Ga]Ga-MALAT-1-antisense oligonucleotides for specific PET imaging of MALAT-1 expressing tumours
Authors: Liu Zhen-Feng , Ye Qian-Ni , Yang Jun , Yang Min , Pan Dong-Hui , Dong Meng-Jie 
Published: February 2021

Objective
The present study was to explore the feasibility of developing positron molecular probes for the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), to evaluate the distribution and pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumours with high MALAT-1 expression in vivo.

Methods
[68Ga]Ga labelling of MALAT-1 antisense oligonucleotides ([68Ga]Ga-MALAT-1-ASO) was synthesized by the conjugation of MALAT-1-NOTA-ASO and [68Ga] Ga3+. The radiochemical purity was shown by radio-HPLC. Pharmacokinetic studies and cellular uptake studies were performed. The biodistribution and metabolism of [68Ga] Ga-MALAT-1-ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied in vitro and in vivo.

Results
[68Ga]Ga-MALAT-1-ASO was obtained in 98% radiochemical yield from a 10-min synthesis with 100 ± 50 MBq/nmol specific activity and >99% radiochemical purity. The Log D was −2.53 ± 0.19. The tracer displayed excellent stability in vitro. 68Ga–MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of [68Ga]Ga-MALAT-1-ASO in MHCC-LM3 tumour-bearing mice demonstrated specific uptake of the radiotracer (3.04 ± 0.11%ID/g). Micro-PET images of the MHCC-LM3 cell xenograft mouse model provided further evidence to support the hypothesis that [68Ga]Ga-MALAT-1-ASO can target tumours in vivo.

Conclusions
We conclude that [68Ga]Ga labelling of MALAT-1 ASO is a convenient approach. The high accumulation of [68Ga]Ga-MALAT-1-ASO for tumours expressing MALAT-1 suggests that this radio compound may be used as a potential positron molecular probe. Molecular structure optimization studies need to be more in-depth to further reduce its background uptake and enhance tumour targeting.
Synthetic human livers for modeling metabolic diseases
Authors: Tafaleng Edgar N. , Malizio Michelle R. , Fox Ira J. , Soto-Gutierrez Alejandro 
Published: February 2021

Purpose of review
In this review, we will explore recent advances in human induced pluripotent stem cell (iPSC)-based modeling of metabolic liver disease and biofabrication of synthetic human liver tissue while also discussing the emerging concept of synthetic biology to generate more physiologically relevant liver disease models.

Recent finding
iPSC-based platforms have facilitated the study of underlying cellular mechanisms and potential therapeutic strategies for a number of metabolic liver diseases. Concurrently, rapid progress in biofabrication and gene editing technologies have led to the generation of human hepatic tissue that more closely mimic the complexity of the liver.

Summary
iPSC-based liver tissue is rapidly becoming available for modeling liver physiology due to its ability to recapitulate the complex three-dimensional architecture of the liver and recapitulate interactions between the different cell types and their surroundings. These mini livers have also been used to recapitulate liver disease pathways using the tools of synthetic biology, such as gene editing, to control gene circuits. Further development in this field will undoubtedly bolster future investigations not only in disease modeling and basic research, but also in personalized medicine and autologous transplantation.
Update on cerebrotendinous xanthomatosis
Authors: DeBarber Andrea E. , Duell P. Barton 
Published: February 2021

Purpose of review
Cerebrotendinous xanthomatosis (CTX) is a rare genetic lipid storage disorder with highly pleomorphic clinical phenotype. Complications of this disease can be devastating and may include severe cognitive impairment and dementia in later stages. Disease progression can be prevented or stabilized by bile acid replacement therapy, although a subset of patients with advanced disease continue to deteriorate despite therapy.

Recent findings
Delayed diagnosis of CTX continues to impede effective treatment. A clinical diagnostic algorithm for CTX was developed that can decrease the age of diagnosis of CTX. The strategy of screening children with bilateral juvenile cataracts for CTX also improved diagnosis, as this group had a 500-fold higher-rate of CTX than the general population. Improved diagnosis of CTX is critical, as patients treated early in the course of the disease have significantly better outcomes compared with those treated later. More sensitive and specific biochemical testing for CTX has been developed that is potentially more informative than blood cholestanol to assess treatment efficacy and medication compliance in CTX.

Summary
Because we are recognizing more severe presentations of CTX in infants and children, and delayed diagnosis and treatment worsens the prognosis, CTX is an excellent candidate disorder for newborn screening using recently reported methods for newborn dried bloodspot analysis.
Measuring Gastric pH in Tube‐fed Children With Neurologic Impairments and Gastroesophageal Disease
Authors: Tjon James , Cooper Mitchell , Pe Michael , Boodhan Sabrina , Mahant Sanjay , Avitzur Yaron , Atenafu Eshetu G. , Moradipour Tassnim , Sepiashvili Lusia , Cohen Eyal 
Published: February 2021

ABSTRACTObjectives:The aim of the study was to determine the extent of agreement between pH paper and handheld pH meter with a laboratory pH meter for gastric pH measurement in children with neurologic impairments and gastrostomy tubes who have gastroesophageal reflux disease (GERD).Methods:In this prospective observational study, gastric contents were aspirated from gastric or nasogastric tubes and the pH measured using 3 techniques: pH paper, handheld pH meter, and laboratory pH meter (the gold standard). Agreement between techniques was assessed with intraclass correlation coefficient (ICC), Bland‐Altman analysis, and kappa statistic.Results:Among 43 patients contributing 67 gastric samples, the ICC was 0.75 (95% confidence interval [CI]: 0.69–0.97) between the handheld and laboratory meters, 0.69 (95% CI: 0.63‐‐0.94) between the pH paper and laboratory meter and 0.69 (95% CI: 0.63–0.94) between the handheld meter and paper. The Bland‐Altman analysis between the handheld and lab meters showed a mean difference of −0.03 pH units (limits of agreement: −0.52 to 0.47 pH units) and 0.17 pH units (limits of agreement: −0.99 to 1.33 pH units) between the paper and lab meter. The kappa coefficients for a pH ≥4 were 1.0 (95% CI: 1.0‐‐1.0) between the handheld and lab meters and 0.9 (95% CI: 0.77‐‐1.0) between the paper and lab meter.Conclusions:The findings suggest that both point‐of‐care tests, the pH meter and pH paper, correlate well with the gold standard for testing pH with a laboratory pH meter, indicating usefulness in point‐of‐care testing for monitoring gastric pH in tube‐fed children with neurologic impairments and GERD.
Reference Values Matter
Authors: Ellemunter Helmut , Dumke Markus , Steinkamp Gratiana 
Published: February 2021

ABSTRACTReference values are important for patient care as well as for comparisons between different centers or countries. We investigated two anthropometric reference datasets, the US Centers for Disease Control (CDC) growth charts and the German Health Interview and Examination Survey for Children and Adolescents Study (KiGGS) percentiles, which were established in Germany between 2003 and 2006. A smaller proportion of children with cystic fibrosis had decreased z scores <−2 with CDC (5.0% for weight and 3.0% for height) compared to KiGGS (7.4% for weight and 6.3% for height) values (P < 0.0001). Median z scores were higher using the CDC reference data. Thus, the choice of growth reference is important, may influence clinical management and must be considered when comparing the outcomes of different institutions.
Impact of Metronidazole Treatment and Dientamoeba Fragilis Colonization on Gut Microbiota Diversity
Authors: Gotfred‐Rasmussen Helle , Stensvold Christen Rune , Ingham Anna Cäcilia , Johannesen Thor Bech , Andersen Lee O'Brien , Röser Dennis , Nielsen Henrik Vedel 
Published: February 2021

ABSTRACTObjectives:The intestinal parasite Dientamoeba fragilis is a common colonizer of children in Denmark. Metronidazole has been used to reduce gastrointestinal symptoms in children colonized with D fragilis. We aimed to identify gut microbiota changes associated with D fragilis carrier status and metronidazole treatment of D fragilis‐positive children.Methods:The fecal microbiota of 275 fecal samples from children treated with metronidazole (n = 48) or placebo (n = 48) were characterized by ribosomal DNA sequencing. Samples collected before (T1), 2 weeks after (T2), and 8 weeks (T5) after treatment were included. Seventy fecal samples from 70 age‐matched parasite‐negative children served as controls.Results:The abundance of 24 bacterial genera differed significantly according to D fragilis carrier status, with Flavonifractor being remarkably more abundant in children testing negative for D fragilis. Eight bacterial genera changed significantly in abundance in children losing versus keeping D fragilis after metronidazole treatment. Of these, 7 returned to pretreatment (T1) levels at T5. Meanwhile, the abundance of Flavonifractor continued to differ at T5, whereas for Ruminococcus the abundance only remained high in children who were D fragilis‐negative at T2 and T5. Increases in Hungatella, Sutterella, and Streptococcus abundances observed at T2 were specific to metronidazole exposure and hence independent of D fragilis colonization.Conclusions:This study revealed that specific bacterial genera were associated with D fragilis colonization. Metronidazole treatment had a short‐term impact on the abundance of some bacterial genera, with most of these reverting to pretreatment levels 8 weeks after completed treatment.
Applying an Age‐specific Definition to Better Characterize Etiologies and Outcomes in Neonatal Acute Liver Failure
Authors: Borovsky Kristin , Banc‐Husu Anna M. , Saul Samantha A. , Neighbors Katie , Kelly Susan , Alonso Estella M. , Taylor Sarah A. 
Published: February 2021

ABSTRACTObjective:Neonatal acute liver failure (ALF) is a rare disease with high mortality for which no standard age‐specific definition exists. To advance the understanding of neonatal ALF, we characterize the etiology, presenting features, treatment, and outcomes in infants within 1 month of life.Methods:We performed a single‐center 11‐year retrospective chart review of neonates ⩽30 days of life with ALF as defined by an INR of ≥2.0. Comparisons were made by etiology and survival with native liver (SNL). Estimated survival was performed using the Kaplan‐Meier method.Results:Forty‐three patients met inclusion criteria for neonatal ALF. Etiologies included viral infection (23%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD‐NH) (21%), cardiac‐associated ischemia (16%), other ischemia (14%), genetic etiologies (9%), Trisomy 21‐associated myelodysplasia (TAM) (7%), hemophagocytic lymphohistiocytosis (HLH) (2%), and not identified (7%). Infants with viral etiologies had the highest alanine aminotransferase (ALT) at presentation (1179 IU/L, interquartile range [IQR] 683–1585 IU/L) in contrast to low levels in GALD‐NH (23 IU/L, IQR 18–64 IU/L). Across all etiologies, only 33% were alive at 1 year. Overall median survival was 74 days; 17 days for viral infection and 74 days for GALD‐NH. Among laboratory values at presentation, alpha‐fetoprotein (AFP) was significantly higher in patients that survived with their native liver (P = 0.04).Conclusions:Overall, outcome for neonatal ALF is poor. Although initial laboratory values can differentiate viral infection or GALD‐NH, further studies are needed to identify laboratory parameters that predict SNL by etiology to ultimately improve patient outcomes.
Nonalcoholic Wernicke-Korsakoff Syndrome Resulting From Psychosis
Authors: Alves Pereira de Carvalho Saraiva Rodrigo , Gonçalves Maria , Sereijo Carolina , Mendes Tiago , Kamyar Rita Barandas , Abreu Manuela , Coentre Ricardo 
Published: February 2021

Abstract
Wernicke encephalopathy (WE) results from thiamine deficiency. If undiagnosed or inadequately treated, WE evolves into Korsakoff syndrome (KS). We herein report a case of nonalcoholic Wernicke-Korsakoff syndrome (WKS) that resulted from malnutrition due to psychosis in a 42-years-old male patient. Thiamine deficiency was secondary to severe malnourishment due to poisoning delusions and daily life disorganization in a patient with previously unrecognized schizophrenia. Besides the presence of WE's classic triad of signs, brain magnetic resonance imaging showed also typical thalamic lesions. Furthermore, the patient also presented anterograde and retrograde amnesia, executive dysfunction, and confabulations, compatible with KS being already present. Intravenous treatment with thiamine was given for 37 days. Improvement in cognitive functions and brain imaging alterations was evident. Nevertheless, persistent WKS deficits were present. This case highlights the multiplicity of etiologies of WKS, namely, psychiatric, and its debilitating consequences if not promptly recognized and treated.
Peri-incisional perfusion does not differ between running versus interrupted Allgöwer-Donati suture technique in ankle fracture surgery: a pilot randomized controlled trial of wound perfusion
Authors: Thamyongkit Sorawut , Luksameearunothai Kitchai , Shafiq Babar , Hasenboehler Erik A. 
Published: February 2021

Abstract

Objectives:
To compare peri-incisional perfusion, perfusion impairment and wound closure time between the conventional interrupted Allgöwer-Donati (IAD) technique and a modified running Allgöwer-Donati (RAD) technique in ankle fracture surgery.

Design:
Prospective, randomized controlled clinical trial.

Setting:
Level I and II trauma centers.

Patients:
Twenty-five healthy adults with ankle fractures (AO/OTA 44-A, 44-B, or 44-C) between November 2017 and December 2018. (Of 26 patients enrolled in this study, 1 was lost to follow-up.)

Intervention:
Participants were randomized into the IAD or the RAD group (13 patients each). All participants were followed for at least 3 months after surgery to assess for wound complications.

Main Outcome Measurements:
Skin perfusion was assessed immediately after wound closure with laser-assisted indocyanine green angiography. Wound closure time, mean incision perfusion, and mean perfusion impairment were measured and compared with analysis of variance. Alpha = 0.05.

Results:
The RAD technique was significantly faster in terms of mean (± standard deviation) wound closure time (6.2 ± 1.4 minutes) compared with the IAD technique (7.3 ± 1.4 minutes) (P = 0.047). We found no differences in mean incision perfusion and mean perfusion impairment (all, P > 0.05).

Conclusion:
The IAD and RAD techniques resulted in similar peri-incisional perfusion and perfusion impairment. Closure time was significantly shorter for the RAD technique compared with the IAD technique.

Level of Evidence:
I
Evaluation of a Portable Wavefront Aberrometer for Community Screening Refraction in the Elderly
Authors: Plum William , Varadaraj Varshini , Dosto Niccolo , Thompson Sean L. , Gajwani Prateek , Friedman David S. 
Published: February 2021

ABSTRACT

SIGNIFICANCE
The SVOne may prove useful to quickly and easily assess refractive correction needs in community screenings and low-resource settings, but not all subjects were testable with the device

PURPOSE
This study aimed to compare the SVOne handheld, smartphone-based wavefront aberrometer with a tabletop autorefractor in identifying refractive errors in elderly subjects.

METHODS
Participants 50 years or older at community eye screenings with visual acuity worse than 20/40 in either eye underwent autorefraction followed by two SVOne trials. Power vectors of right eye data were analyzed.

RESULTS
Of 84 subjects who underwent autorefraction, 67 (79.8%) were successfully autorefracted with the SVOne, of whom 82.1% (55/67) had a successful repeat reading. Mean M (spherical equivalent) values from tabletop and handheld autorefraction were −0.21 D (95% confidence interval [CI], −0.71 to +0.29 D) and −0.29 D (95% CI, −0.79 to +0.21 D), respectively (P > .05). Mean astigmatism values from tabletop and handheld devices were +1.06 D (95% CI, 0.87 to 1.26 D) and +1.21 D (95% CI, 0.99 to 1.43 D), respectively (P > .05). Intraclass correlation coefficients between devices were 0.95 (95% CI, 0.93 to 0.97) for M, 0.78 (95% CI, 0.66 to 0.86) for J
0, and 0.45 (95% CI, 0.24 to 0.63) for J
45 (P < .05 for all). Excellent test-retest correlation between SVOne measurements was noted for M (Pearson correlation [r] = 0.96; P < .05), but a weaker correlation was noted for J
0 and J
45 (r = 0.67 and r = 0.63 [P < .05 for both], respectively).

CONCLUSIONS
The SVOne provided strong agreement for M, with the majority of readings within ±1.00 D of each other, when compared with the tabletop autorefractor. A weaker but still good correlation was noted for astigmatism. Similar findings were noted when assessing repeatability.
The Effect of Continuous Passive Motion in Patients Treated With Total Knee Arthroplasty for Osteoarthritis
Authors: Yang Ying , Wang Jing , Zhang Xiao-yu , Dong Li , Liu Ai-feng , Li Chun-yue 
Published: February 2021

Objective
The aim of the study was to identify the effectiveness of the continuous passive motion application on clinical outcomes after total knee arthroplasty, based on evidence from recently published high-quality randomized controlled trials.

Design
Two reviewers retrieved platforms of PubMed, Embase, and CENTRAL independently, for identifying eligible randomized controlled trials evaluating the effect of continuous passive motion applied after total knee arthroplasty for knee osteoarthritis. Subgroup meta-analyses were performed for all syntheses based on the follow-up intervals.

Results
A total of 10 randomized controlled trials, involving 841 patients, were finally included. Data were available for 15 different outcomes (including active/passive knee extension/flexion/full range of motion, Western Ontario and McMaster Universities Osteoarthritis Index–pain/physical function/stiffness/total score, visual analogue scale, time up and go, knee girth, Knee Society Scale-function/knee score), at several time points. In general, most of the pools demonstrated similar outcome between continuous passive motion and noncontinuous passive motion groups. Exclusively, the active knee extension at 1 wk (mean difference = 3.00, 95% confidence interval = 0.5–5.5, P = 0.019*), passive knee extension at 1 wk (mean difference = 3.00, 95% confidence interval = 0.28–5.72, P = 0.031*), and 3 mos (mean difference = 3.00, 95% confidence interval = 0.5–5.5, P = 0.019*) were shown to be significantly slightly different between two groups.

Conclusions
This study demonstrated a limited role of continuous passive motion in patients operated with total knee arthroplasty. Thus, there is at this stage no indication for continuous passive motion procedures in patients operated with total knee arthroplasty as a standard postoperative care.
Musculoskeletal Ultrasound as a Motivator for Selecting a Physical Medicine and Rehabilitation Residency Program in the United States
Authors: Raja Altamash E. , Shustorovich Alexander , Robinson David M. , Alfonso Kathryn , Meyer Ryan , Roemmich Ryan T. , Eng Christine , Wisniewski Steve J. , Cabahug Philippines 
Published: February 2021

Abstract
This study aimed to determine the influence of musculoskeletal ultrasound (MSKUS) curriculum on applicants during the residency-selection process. A survey of 666 applicants for the Johns Hopkins University, Mayo Clinic, and Harvard/Spaulding Rehabilitation Physical Medicine and Rehabilitation programs was conducted in June 2020. A total of 180 respondents scored the influence of a MSKUS curriculum on their decision making for residency selection. In addition, applicants were asked to rank specific areas of physical medicine and rehabilitation that influenced their decision making. Participants most commonly included MSKUS in their top three areas of interest when constructing their rank order list. When asked whether MSKUS presence within a program had an effect during the interview-selection process, 71% responded with “very important” or “absolutely essential” (P < 0.001). For 74% of applicants, exposure to MSKUS in residency was an important factor when creating their rank order list (P < 0.001). More than 92% of applicants stated that they are “likely” or “very likely” to use MSKUS in their future practice and 83% would recommend a program with MSKUS to future candidates (P < 0.001). Based on these results, a large percentage of physical medicine and rehabilitation applicants intend on using MSKUS in their future practice. Therefore, MSKUS may be an important factor for residency selection.
Instructional Cueing Alters Upper Limb Muscle Activity and Kinematics During Elastic Resistance Exercise
Authors: Reece Ashley A. , Parkinson James E. , Cudlip Alan C. , Page Phil , Holmes Michael W.R. 
Published: February 2021

Objective
The purpose of this study was to quantify the differences in upper limb muscle activity and kinematics when performing shoulder elastic resistance exercises with no cue, slouched posture, and corrected posture.

Design
Fifteen healthy participants completed four shoulder elastic resistance exercises (unilateral flexion, bilateral flexion, external rotation, and external rotation with towel) across three simulated body postures (no cue, corrected posture, and slouched posture). Surface electromyography was measured on 16 upper limb muscles and kinematics were collected. Two-way repeated-measures analyses of variance examined differences in muscle activation and kinematics across postures and exercises.

Results
Interactions between exercise and posture were found for most muscles. Muscle activity interactions existed in 14 of the 16 muscles examined, with 8 muscles having the greatest activity in the unilateral flexion, slouched condition (P < 0.0001). The slouched posture generated activity up to 88.4 ± 5.1 %MVC in the cervical extensors. Completing flexion or external rotation exercises with a slouched posture led to increased glenohumeral range of motion (P < 0.0001), but these differences were less than 5 degrees between the greatest and smallest ranges of motion (85.8 vs. 81.0 degrees).

Conclusion
Posture influenced muscle activation and kinematics, with slouched postures increasing muscle activity and range of motion. There was little to no difference between the no cue and corrected cue conditions, suggesting that perhaps a clinician’s time may be better spent focusing on avoiding slouched postures rather than ensuring mastering technique.