bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectrum of Mutations in NDP Resulting in Ocular Disease; a Systematic Review
Authors: Wawrzynski James , Patel Aara , Badran Abdul , Dowell Isaac , Henderson Robert , Sowden Jane C. 
Published: May 2022

Aims and Rationale: The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR). However, little is known about whether the nature or location of the NDP variant is predictive of severity. In this systematic review we summarise all reported NDP variants and draw conclusions about whether the nature of the NDP variant is predictive of the severity of the resulting ocular pathology and associated hearing loss and intellectual disability.Findings: 201 different variants in the NDP gene have been reported as disease-causing. The pathological phenotype that may result from a disease-causing NDP variant is quite diverse but generally comprises a consistent cluster of features (retinal hypovascularisation, exudation, persistent foetal vasculature, tractional/exudative retinal detachment, intellectual disability and hearing loss) that vary predictably with severity. Previous reviews have found no clear pattern in the nature of NDP mutations that cause either FEVR or Norrie disease, with the exception that mutations affecting cysteine residues have been associated with Norrie Disease and that visual loss amongst patients with Norrie disease tends to be more severe if the NDP mutation results in an early termination of translation as opposed to a missense related amino acid change. A key limitation of previous reviews has been variability in the case definition of Norrie disease and FEVR amongst authors. We thus reclassified patients into two groups based only on the severity of their retinal disease. Of the reported pathogenic variants that have been described in more than one patient, we found that any given variant caused an equivalent severity of retinopathy each time it was reported with very few exceptions. We therefore conclude that specific NDP mutations generally result in a consistent retinal phenotype each time they arise. Reports by different authors of the same variant causing either FEVR or Norrie disease conflict primarily due to variability in the authors’ respective case definitions rather than true differences in disease severity.
Half-Life Extended Nanobody-Based CD38-Specific Bispecific Killercell Engagers Induce Killing of Multiple Myeloma Cells
Authors: Hambach Julia , Fumey William , Stähler Tobias , Gebhardt Anna Josephine , Adam Gerhard , Weisel Katja , Koch-Nolte Friedrich , Bannas Peter 
Published: May 2022

CD38 is a target for immunotherapy of multiple myeloma. Llama-derived CD38-specific nanobodies allow easy reformatting into mono-, bi- and multispecific proteins. To evaluate the utility of nanobodies for constructing CD38-specific nanobody-based killer cell engagers (nano-BiKEs), we generated half-life extended nano-BiKEs (HLE-nano-BiKEs) by fusing a CD38-specific nanobody to a CD16-specific nanobody for binding to the Fc-receptor on NK cells and further to an albumin-specific nanobody to extend the half-life in vivo. HLE-nano-BiKEs targeting three different epitopes (E1, E2, E3) of CD38 were expressed in transiently transfected HEK-6E cells. We verified specific and simultaneous binding to CD38 on myeloma cells, CD16 on NK cells, and to albumin. We tested the capacity of these HLE-nano-BiKEs to mediate cytotoxicity against CD38-expressing multiple myeloma cell lines and primary myeloma cells from human bone marrow biopsies in bioluminescence and flowcytometry assays with NK92 cells as effector cells. The results revealed specific time- and dose-dependent cytolysis of CD38+ myeloma cell lines and effective depletion of CD38-expressing multiple myeloma cells from primary human bone marrow samples. Our results demonstrate the efficacy of CD38-specific HLE-nano-BiKEs in vitro and ex vivo, warranting further preclinical evaluation in vivo of their therapeutic potential for the treatment of multiple myeloma.
Sustainable Alkali-Activated Slag Binders Based on Alternative Activators Sourced From Mineral Wool and Glass Waste
Authors: Pavlin Majda , König Katja , König Jakob , Javornik Uroš , Ducman Vilma 
Published: May 2022

In the present study, four different locally available waste glass materials (bottle glass-BG, glass wool-GW, stone wool-SW and cathode-ray tube glass-CRTG) were treated with hot concentrated potassium hydroxide (KOH) in order to obtain alternative alkali activators (AAAs). We evaluated the suitability of the solutions obtained for use as AAAs in the production of AAMs. AAMs were prepared using electric arc furnace slag and selected AAAs with a higher content of dissolved Si. We evaluated the performance of the AAMs in comparison to that of slags activated with KOH or potassium-silicate (K-silicate). The compressive strength of the AAMs prepared with KOH-based AAAs were high when Si and Al were simultaneously abundant in the AAA (9.47 MPa when using the activator sourced from the CRTG), and low with the addition of KOH alone (1.97 MPa). The AAM produced using commercial K-silicate yielded the highest compressive strength (27.7 MPa). The porosity of the KOH-based AAM was lowest when an alternative BG-based activator was used (24.1%), when it was similar to that of the AAM prepared with a K-silicate. The BG-based activator had the highest silicon content (33.1 g/L), and NMR revealed that Si was present in the form of Q0, Q1 and Q2. The concentrations of toxic trace elements in the AAAs used for alkali activation of the slag were also determined, and leaching experiments were performed on the AAMs to evaluate the immobilisation potential of alkali-activated slag. In the SW AAAs the results show acceptable concentrations of trace and minor elements with respect to the regulations on waste disposal sites, while in the activators prepared from BG, CRTG and GW some elements exceeded the allowable limits (Pb, Ba, Sb, and As).
Medical Humanities Education and Its Influence on Students' Outcomes in Taiwan: A Systematic Review
Authors: Hoang Bao Lan , Monrouxe Lynn Valerie , Chen Kuo-Su , Chang Shu-Ching , Chiavaroli Neville , Mauludina Yosika Septi , Huang Chien-Da 
Published: May 2022

BackgroundMedical education has emphasized the importance of integrating medical humanities training into the curriculum to benefit medical and nursing students' future practice, featuring in the list of national funding priorities for healthcare education research in Taiwan for many years. However, the extent to which this drive has resulted in medical humanities training, what rationales underpin its inclusion, and its efficacy is largely unknown. This study aims to address these issues across medical humanities programs within the Taiwanese context.MethodsWe conducted a systematic review. Inclusion criteria included studies in English or Mandarin reporting outcomes of medical humanities courses in healthcare education settings in Taiwan between 2000 and 2019. We searched across five electronic databases (PubMed, Embase, ERIC, PsycInfo, Web of Science), following PRISMA guidelines. The Best Evidence Medical Education (BEME) Global Scale and Kirkpatrick Levels are used for identifying the strength of evidence.Results17 articles were extracted from the 134 identified. Intrinsic and instrumental rationales for the inclusion of medical humanities education were common, compared with epistemological-based and critical-based approaches. Several positive impacts were identified in relation to participation including modification of attitudes, knowledge, and skills. However, the highest level (i.e., unequivocal) of evidence characterized by effects on students' behaviors or ongoing interaction with colleagues and patients is lacking.ConclusionFindings suggest that although medical humanities education is widely implemented in Taiwan, no clear consensus has been reached regarding the rationale for inclusion or how it is localized from Western to Asian contexts. Future research still needs to explore the long-term impact of medical humanities education for medical and nursing students and its impact on patient care.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier: CRD42019123967.
Biomechanical Considerations of Patching Material for Posterior Scleral Reinforcement Surgery
Authors: Ma Jinlei , Wu Fangyuan , Liu Zhiyong , Fang Yijiong , Chu Xu , Zheng Linyan , Xue Anquan , Nan Kaihui , Qu Jia , Cheng Lingyun 
Published: May 2022

PurposeTo characterize biomechanical properties of genipin-crosslinked human dura mater as reinforcing material for posterior scleral reinforcement (PSR) and to compare it with crosslinked human sclera.MethodsDonor dura mater and sclera were crosslinked in the same optimized genipin solution. Resistance to enzyme degradation for both materials were investigated by exposing the materials to accelerated enzyme degrading. Elastic modulus and tensile strength were measured by biomechanics testing equipment. Crosslinked human dura mater was used as reinforcing patch in PSR on 57 adult pathologic myopic eyes. The patients were followed up for an average 3 years. The main outcome was eye globe axial length change and safety profile of the reinforcing material.ResultsCrosslinked dura mater demonstrated similar percentage weight loss to crosslinked sclera when exposed to enzymatic solution. Dura mater has higher density than sclera. The retaining elastic modulus after enzyme exposure was 72.02 MPa for crosslinked dura mater while 53.88 MPa for crosslinked sclera, 34% greater for crosslinked dura mater, P = 0.0186). At the end of 3 years follow-up, the mean globe axis of the surgery eyes was reduced by 1.29 mm (from 30.81 to 29.51 mm, P &lt; 0.0001, paired t-test). Visual acuity (BCVA logMar) improved by 0.10 logMar unit which is an improvement of five letters (P = 0.0184, paired t-test). No material specific complication was noted.ConclusionCrosslinked human dura mater may be superior to crosslinked human sclera as reinforcing material for PSR to manage progression of high myopia. This material was well tolerated on human eye.
Clinical Outcomes and Microbiological Characteristics of Sequence Type 11 Klebsiella pneumoniae Infection
Authors: Yang Ping , Wu Zhenchao , Liu Chao , Zheng Jiajia , Wu Nan , Wu Zhangli , Yi Juan , Lu Ming , Shen Ning 
Published: May 2022

BackgroundSequence type 11 (ST11) Klebsiella pneumoniae (Kp) is highly prevalent in China and is a typical sequence type among KPC-producing isolates. This study aimed to evaluate the clinical outcomes and microbiological features of ST11 Kp infections.MethodsA retrospective cohort study was conducted at Peking University Third Hospital from January 2017 to March 2021. Clinical data were collected from medical records. Antimicrobial susceptibility testing and string tests were performed. Whole-genome sequencing was used to analyze the capsular serotypes, detect virulence-associated genes, and perform multilocus sequence typing. The risk of all-cause mortality in ST11 Kp-infected patients was compared to that in non-ST11 Kp-infected patients.ResultsFrom 139 patients infected with Kp, 49 ST11 Kp (35.3%) strains were isolated. The Charlson comorbidity index in the ST11 group was higher than that in the non-ST11 group (3.94 ± 1.59 vs. 2.41 ± 1.54, P = 0.001). A greater number of ST11 Kp-infected patients required ICU admission (46.9 vs. 16.7%, P &lt; 0.001) and mechanical ventilation (28.6 vs. 10.0%, P = 0.005). All ST11 isolates presented a multidrug-resistant (MDR) phenotype, and twenty-nine (59.2%) hypervirulent Kp (hvKp) were identified. Twenty-four ST11 strains presented with hypermucoviscosity. The presence of capsular types K47 and K64 was frequent in the ST11 Kp strains (P &lt; 0.001). The key virulence-associated genes rmpA, rmpA2, iucA, iroB, and peg344 were present in 26.5, 42.9, 59.2, 0, and 26.5% of the isolates, respectively, in the ST11 group. Twenty-one ST11 isolates harbored the combination of iucA+rmpA2. The 30-day mortality rate and sequential organ failure assessment (SOFA) score were significantly higher in ST11 Kp-infected patients than in non-ST11 Kp-infected patients (P &lt; 0.01). ST11 Kp infection appeared to be an independent risk factor for mortality in ST11 Kp-infected patients.ConclusionsA high prevalence of the ST11 clone was found in the hospital, which accounted for elevated antimicrobial resistance and exhibited great molecularly inferred virulence. Patients with ST11 Kp infection had a tendency toward increased 30-day mortality and SOFA scores. ST11 Kp infection was an independent risk factor for mortality, suggesting that enhanced surveillance and management are essential.
Characterization of Mild and Moderate Dysarthria in Parkinson’s Disease: Behavioral Measures and Neural Correlates
Authors: Steurer Hanna , Schalling Ellika , Franzén Erika , Albrecht Franziska 
Published: May 2022

PurposeAlterations in speech and voice are among the most common symptoms in Parkinson’s disease (PD), often resulting in motor speech disorders such as hypokinetic dysarthria. We investigated dysarthria, verbal fluency, executive functions, and global cognitive function in relation to structural and resting-state brain changes in people with PD.MethodsParticipants with mild-moderate PD (n = 83) were recruited within a randomized controlled trial and divided into groups with varying degrees of dysarthria: no dysarthria (noDPD), mild dysarthria (mildDPD), moderate dysarthria (modDPD), and also combined mildDPD and modDPD into one group (totDPD). Voice sound level and dysphonia, verbal fluency, motor symptoms, executive functions, disease severity, global cognition, and neuroimaging were compared between groups. Gray matter volume and intensity of spontaneous brain activity were analyzed. Additionally, regressions between behavioral and neuroimaging data were performed.ResultsThe groups differed significantly in mean voice sound level, dysphonia, and motor symptom severity. Comparing different severity levels of dysarthria to noDPD, groups differed focally in resting-state activity, but not in brain structure. In totDPD, lower scores on semantic verbal fluency, a composite score of executive functions, and global cognition correlated with lower superior temporal gyrus volume.ConclusionThis study shows that severity of dysarthria may be related to underlying structural and resting-state brain alterations in PD as well as behavioral changes. Further, the superior temporal gyrus may play an important role in executive functions, language, and global cognition in people with PD and dysarthria.
Sentence Comprehension in Primary Progressive Aphasia: A Study of the Application of the Brazilian Version of the Test for the Reception of Grammar (TROG2-Br)
Authors: Carthery-Goulart Maria Teresa , de Oliveira Rosimeire , de Almeida Isabel Junqueira , Campanha Aline , da Silva Souza Dayse , Zana Yossi , Caramelli Paulo , Machado Thais Helena 
Published: May 2022

Sentence-comprehension deficits have been described in patients with primary progressive aphasia (PPA). However, most instruments to address this domain in more detail and in a clinical context have not been adapted and translated into several languages, posing limitations to clinical practice and cross-language research.ObjectivesThe study aimed to (1) test the applicability of the Brazilian version of the Test for Reception of Grammar (TROG2-Br) to detect morphosyntactic deficits in patients with PPA; (2) investigate the association between performance in the test and sociodemographic and clinical variables (age, years of formal education, and disease duration); (3) characterize the performance of individuals presenting with the three more common variants of PPA (non-fluent, semantic, and logopenic) and mixed PPA (PPA-Mx) and analyze whether TROG-2 may assist in the distinction of these clinical profiles.MethodsA total of 74 cognitively healthy participants and 34 individuals diagnosed with PPA were assessed with TROG2-Br. Overall scores (correct items, passed blocks), types, and categories of errors were analyzed.ResultsIn controls, block scores were significantly correlated with years of formal education (Spearman'sr= 0.33,p= 004) but not with age. In PPA, age, education, and disease duration were not significantly associated with performance in the test. Controls presented a significantly higher performance on TROG2-Br compared to PPA individuals and their errors pattern pointed to mild general cognitive processing difficulties (attention, working memory). PPA error types pointed to processing and morphosyntactic deficits in nonfluent or agrammatic PPA, (PPA-NF/A), logopenic PPA (PPA-L), and PPA-Mx. The semantic PPA (PPA-S) subgroup was qualitatively more similar to controls (processing difficulties and lower percentage of morphosyntactic errors). TROG2-Br presented good internal consistency and concurrent validity.DiscussionOur results corroborate findings with TROG-2 in other populations. The performance of typical older adults with heterogeneous levels of education is discussed along with recommendations for clinical use of the test and future directions of research.
Comparison of the Results of a Parkinson's Holter Monitor With Patient Diaries, in Real Conditions of Use: A Sub-analysis of the MoMoPa-EC Clinical Trial
Authors: Pérez-López Carlos , Hernández-Vara Jorge , Caballol Nuria , Bayes Àngels , Buongiorno Mariateresa , Lopez-Ariztegui Núria , Gironell Alexandre , López-Sánchez José , Martínez-Castrillo Juan Carlos , Sauco M Alvarez , López-Manzanares Lydia , Escalante-Arroyo Sonia , Pérez-Martínez David A. , Rodríguez-Molinero Alejandro ,   The MoMoPa-EC Research Group
Published: May 2022

BackgroundFor specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools—Sense4Care's STAT-ON—can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed.MethodsEighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data.ResultsThe intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3–0.73) for the OFF time (%), 0.48 (95% CI: 0.17–0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44–0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was −0.63 (p&lt; 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS.ConclusionThis sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary.Trial Registrationhttps://clinicaltrials.gov/show/NCT04176302(NCT04176302).
Physiological Mechanisms and Significance of Intracranial B Waves
Authors: Newell David W. , Nedergaard Maiken , Aaslid Rune 
Published: May 2022

ObjectiveRecently published studies have described slow spontaneous cerebral blood flow (CBF) and cerebrospinal fluid (CSF) oscillations measured by magnetic resonance imaging (MRI) as potential drivers of brain glymphatic flow, with a similar frequency as intracranial B-waves. Aiming to establish the relationship between these waveforms, we performed additional analysis of frequency and waveform parameters, of our previously published transcranial Doppler (TCD) and intracranial pressure (ICP) recordings of intracranial B waves, to compare to published MRI frequency measurements of CBF and CSF slow oscillations.Patients and MethodsWe analyzed digital recordings of B waves in 29 patients with head injury, including middle cerebral artery (MCA) flow velocity (FV), ICP, end tidal CO2, and arterial blood pressure (ABP). A subset of these recordings demonstrated high B wave activity and was further analyzed for parameters including frequency, interaction, and waveform distribution curve features. These measures were compared to published similar measurements of spontaneous CBF and CSF fluctuations evaluated using MRI.ResultsIn patients with at least 10% amplitude B wave activity, the MCA blood flow velocity oscillations comprising the B waves, had a maximum amplitude at 0.0245 Hz, and time derivative a maximum amplitude at 0.035 Hz. The frequency range of the B waves was between 0.6–2.3 cycles per min (0.011-0.038 Hz), which is in the same range as MRI measured CBF slow oscillations, reported in human volunteers. Waveform asymmetry in MCA velocity and ICP cycles during B waves, was also similar to published MRI measured CBF slow oscillations. Cross-correlation analysis showed equivalent time derivatives of FV vs. ICP in B waves, compared to MRI measured CBF slow oscillations vs. CSF flow fluctuations.ConclusionsThe TCD and ICP recordings of intracranial B waves show a similar frequency range as CBF and CSF flow oscillations measured using MRI, and share other unique morphological wave features. These findings strongly suggest a common physiological mechanism underlying the two classes of phenomena. The slow blood flow and volume oscillations causing intracranial B waves appear to be part of a cascade that may provide a significant driving force for compartmentalized CSF movement and facilitate glymphatic flow.