bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Term Efficacy and Safety of Open Conjunctiva Ab Externo XEN45 Gel Stent Implantation in Glaucoma Patients
Authors: Thatcher Mitchell D. , Coupal Dustin J. , Cheng Yanzhao , Podbielski Dominik W. 
Published: June 2022

Précis:
We examined the safety and efficacy of the open conjunctiva ab externo approach for XEN45 gel stent implantation. There was a significant reduction in intraocular pressure (IOP) and number of glaucoma medications at 12 months follow-up.

Purpose:
This study aims to determine the safety and efficacy of the open conjunctiva ab externo approach to XEN45 stent implantation.

Materials and Methods:
Retrospective chart review of all patients between July 2018 and March 2020 who underwent XEN45 implantation. IOP and the number of glaucoma medications were measured at the preoperative, 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months postoperative appointments. The primary outcome of this study is the number of cases achieving complete success at 12 months postoperatively.

Results:
Forty-four eyes of 44 patients were included. Mean preoperative IOP was 26.2±8.7 mm Hg on 3.2±0.7 IOP-lowering medications. At 12 months postoperative, mean IOP was 18.9±9.1 mm Hg (n=35, P<0.0001; mean reduction of 27.9%) on 0.9±1.4 (n=35, P<0.0001) IOP-lowering medications. Postoperative needling was performed in 5 cases (11.4%). Of the 35 cases with a postoperative visit at 12 months, complete success was achieved in 14 cases (40.0%) and qualified success in 3 cases (8.6%). Eighteen cases (51.4%) were recorded as failures at 12 months, comprised of 4 cases requiring reoperation for glaucoma (2 XEN45 implants, 1 trabeculectomy, and 1 Baerveldt implant), and 14 cases that did not meet the IOP-lowering criteria for success. During the postoperative course, there was 1 case of self-limited hypotony, 2 self-resolving choroidal effusions, and 3 cases of bleb leakage.

Conclusions:
The open conjunctiva ab externo approach to XEN45 implantation achieved successful levels of IOP reduction in 48.6% of glaucoma cases within the first year. The most common adverse events included the need for additional glaucoma surgery (excluding needling procedures), transient hypotony, and bleb leak.
Neural mechanisms underlying the conditioned pain modulation response: a narrative review of neuroimaging studies
Authors: Nahman-Averbuch Hadas , Timmers Inge 
Published: June 2022

Abstract
Processing spatially distributed nociceptive information is critical for survival. The conditioned pain modulation (CPM) response has become a common psychophysical test to examine pain modulation capabilities related to spatial filtering of nociceptive information. Neuroimaging studies have been conducted to elucidate the neural mechanisms underlying the CPM response in health and chronic pain states, yet their findings have not been critically reviewed and synthesized before. This narrative review presents a simplified overview of MRI methodology in relation to CPM assessments and summarizes the findings of neuroimaging studies on the CPM response. The summary includes functional MRI studies assessing CPM responses during scanning as well as functional and structural MRI studies correlating indices with CPM responses assessed outside of the scanner. The findings are discussed in relation to the suggested mechanisms for the CPM response. A better understanding of neural mechanisms underlying spatial processing of nociceptive information could advance both pain research and clinical use of the CPM response as a marker or a treatment target.
The Role of Bronchoscopy in the Management of Children With Cystic Fibrosis
Authors: Tosco Antonella , Poli Piercarlo , Casale Alida , De Gregorio Fabiola , Sepe Angela , Buonpensiero Paolo , Di Pasqua Antonio , Castaldo Alice , Cimbalo Chiara , Buzzetti Roberto , Raia Valeria , Berlucchi Marco , Timpano Silviana , Badolato Raffaele , Padoan Rita , Orlando Claudio 
Published: June 2022

Background:
Currently, no consensus guidelines recommend routine bronchoscopy procedure in cystic fibrosis (CF), as no evidence is available concerning its use as either a diagnostic or therapeutic tool. Its efficacy is controversial, and no randomized controlled prospective trials are available to check its effectiveness. The aims of the present study were to evaluate the effectiveness of bronchoscopy as a diagnostic/therapeutic tool in CF children and adolescents; and to verify the effect of serial bronchoscopy on lung disease progression in subjects with CF not responding to a single procedure.

Methods:
Data of patients who received bronchoscopy at 2 Italian CF centers were collected. Bronchoalveolar lavage was performed during the procedure including airway clearance with mucolytics, inhaled antibiotics, and/or surfactant instillation.

Results:
A total of 16 patients in center 1 and 17 in center 2 underwent, respectively, 28 and 23 bronchoscopic procedure in the study period. Five patients in each center underwent >1 procedure. All procedures were generally well tolerated. No patient required admission to the pediatric intensive therapy unit. In 19.6% of bronchoalveolar lavages, growth of Aspergillus fumigatus was evident, although not detected by sputum analyses. After the procedure, an increase in mean percent predicted forced expiratory volume in the 1 second >10% was observed, and a significant decrease in pulmonary exacerbations yearly was evident.

Conclusion:
Based on the results, we suggest bronchoscopy is not to be considered an obsolete tool, and it remains useful in CF management, although in selected cases. We encourage to support longitudinal observational studies to standardize the procedure, focusing on the choice of drugs to be instilled, modalities and timing of serial bronchoscopy and subsequent follow-up in selected severe clinical conditions.
Clinical Features of Pancreatic Neuroendocrine Microadenoma
Authors: Okawa Yuki , Tsuchikawa Takahiro , Hatanaka Kanako C. , Matsui Aya , Tanaka Kimitaka , Nakanishi Yoshitsugu , Asano Toshimichi , Noji Takehiro , Nakamura Toru , Mitsuhashi Tomoko , Okamura Keisuke , Hatanaka Yutaka , Hirano Satoshi 
Published: June 2022

Objectives
Pancreatic neuroendocrine microadenoma (NEMA) is a nonfunctioning neuroendocrine tumor of less than 5 mm. Most studies of NEMA were based on autopsies, and few reports have revealed the clinical frequency of NEMA. We investigated the clinicopathological features of NEMA.

Methods
The pathological results of the pancreatic resection specimens of patients, older than 18 years, who underwent pancreatic resection at Hokkaido University Hospital between April 2008 and December 2020 were retrospectively reviewed. The NEMAs were re-examined in detail and examined by immunohistochemical staining.

Results
Among 850 patients enrolled in this study, 24 NEMAs were identified in 12 patients (1.4%). Of the 12 patients, 2 patients had multiple endocrine neoplasia type 1, and the others had no hereditary disease, including 2 patients with multiple NEMAs. A difference in the number of NEMA was observed between patients with multiple endocrine neoplasia type 1 and sporadic NEMA. Intratumoral Ki-67 heterogeneity was correlated with the Ki-67 index. One grade 2 NEMA (Ki-67 index, 4.6%) was detected, but ATRX and DAXX labeling showed intact nuclear protein expression.

Conclusions
Multiple sporadic NEMAs and grade 2 NEMAs were observed, suggesting that NEMA may have malignant potential. Thus, NEMAs should be carefully monitored for lymph node metastasis and postoperative recurrence.
Pediatric Extracranial Germ Cell Tumors: Expression of microRNA
Authors: Saliyeva Symbat , Boranbayeva Riza , Konoplya Natalya , Bulegenova Minira , Blau Olga , Belousov Vyacheslav , Granica Joanna , Mukushkina Dina , Altynbayeva Gulmira 
Published: June 2022

Background:
Germ cell tumors (GCTs) may occur from the neonatal period to late adulthood, characterized by extensive clinical and pathologic heterogeneity. MicroRNAs are a family of small noncoding RNAs that regulate a wide array of biological processes including carcinogenesis. MicroRNAs may be used for many purposes in clinical diagnostics. Numerous studies have proven the diagnostic value of microRNA371-373 and microRNA302/367 expression in malignant GCT. The diagnostic value of microRNA375 is disputable, because while its value is confirmed by some research data, there are still others denying it.

Methods:
The results of our own research on the relative expression of 10 microRNAs, including microRNA375, associated with GCT in the tumor tissues of 84 children and adolescents are presented.

Results:
In our research, overexpression of microRNA 371-373, 302/367 detected in the group of malignant GCT subtypes. Statistically significant expression of microRNA375 have been defined not only in the group of malignant GCT subtypes, but also in the group of immature teratomas. Among malignant GCTs, high expression of microRNA375 is specific for yolk sac tumors. In the group of seminomas, embryonic carcinomas, and mature teratomas expression of microRNA375 was observed imperceptible, even so the results were statistically insignificant.

Conclusion:
Expression of microRNA 371-373, 302/367 is representative of malignant GCT subtypes. Statistically significant and high expression of microRNA375 attributable for yolk sac tumors and immature teratomas.
WHY QUESTIONNAIRE SCORES ARE NOT MEASURES: A QUESTION-RAISING ARTICLE
Authors: Tesio Luigi , Scarano Stefano , Hassan Samah , Kumbhare Dinesh , Caronni Antonio 
Published: June 2022

ABSTRACT
Any person is provided by characteristics that can be neither located in body parts nor directly observed (so-called "latent" variables): these may be behaviors, attitudes, perceptions, motor and cognitive skills, knowledge, emotions, and the like. PRM frequently faces variables of this kind, the target of many interventions. Latent variables can only be observed through representative behaviors (e.g., walking for independence, moaning for pain, social isolation for depression, etc.). To measure them, behaviors are often listed and summated as items in cumulative questionnaires ("scales"). Questionnaires ultimately provide observations ("raw scores") with the aspect of numbers. Unfortunately, they are only a rough and often misleading approximation to true measures for various reasons. Measures should satisfy the same measurement axioms of physical sciences. In the present article, the flaws hidden in questionnaires' scores are summarised, and their consequences in outcome assessment are highlighted. The report should inspire a critical attitude in the readers and foster the interest in modern item response theory, with reference to Rasch analysis.
Efficacy and Safety of Biologic Agents for Lupus Nephritis
Authors: Chen Pang , Zhou Yadong , Wu Lianghua , Chen Shihan , Han Fangduo 
Published: June 2022

Objectives
The aim of this study was to examine the effect and safety of biological agents for lupus nephritis (LN).

Methods
PubMed, EMBASE, and the Cochrane Library databases were searched from their inception up to November 2021. The outcomes were overall response, complete remission, proteinuria, renal activity index, and adverse events (AEs). Only randomized controlled trials (RCTs) were included.

Results
Nine RCTs (1645 patients) were included. The RCTs evaluated abatacept (n = 2), belimumab (n = 1), obinutuzumab (n = 1), atacicept (n = 1), IL-2 (n = 1), ocrelizumab (n = 1), and rituximab (n = 2). The use of biological agents was associated with higher likelihoods of achieving an overall response (relative risk [RR], 1.26; 95% confidence interval [CI], 1.15–1.39; p < 0.001; I
2 = 14.3%; p
Q = 0.301) and a complete response (RR, 1.33; 95% CI, 1.16–1.54; p < 0.001; I
2 = 41.8%; p
Q = 0.056). The use of biological agents was not associated with improvements in the urinary protein-to-creatinine ratio (weighted mean difference, 3.83; 95% CI, −3.71 to 11.38; p = 0.319; I
2 = 99.4%; p
Q < 0.001). The use of biological agents in patients with LN was also not associated with an increased risk of any AEs (RR, 1.01; 95% CI, 0.98–1.04; p = 0.519; I
2 = 0.0%; p
Q = 0.533), serious AEs (RR, 0.95; 95% CI, 0.82–1.09; p = 0.457; I
2 = 0.0%; p
Q = 0.667), grade >3 AEs (RR, 0.91; 95% CI, 0.67–1.22; p = 0.522; I
2 = 0.0%; p
Q = 0.977), infections (RR, 1.09; 95% CI, 0.99–1.20; p = 0.084; I
2 = 0.0%; p
Q = 0.430), and deaths (RR, 0.67; 95% CI, 0.36–1.24; p = 0.200; I
2 = 0.0%; p
Q = 0.439). The meta-regression analysis showed that follow-up duration and the sample size did not influence the complete response rate, whereas publications in 2012 to 2014 influence the rate compared with 2015 to 2020.

Conclusions
Biological agents seem to be effective and safe for managing patients with LN.
Dose Reduction and Image Quality in Photon-counting Detector High-resolution Computed Tomography of the Chest
Authors: Graafen Dirk , Emrich Tilman , Halfmann Moritz C. , Mildenberger Peter , Düber Christoph , Yang Yang , Othman Ahmed E. , O’ Doherty Jim , Müller Lukas , Kloeckner Roman 
Published: June 2022

Purpose:
Photon-counting detector computed tomography (PCD-CT) has the potential to significantly improve CT imaging in many ways including, but not limited to, low-dose high-resolution CT (HRCT) of the lung. The aim of this study was to perform an intrapatient comparison of the radiation dose and image quality of PCD-CT compared with conventional energy-integrating detector CT (EID-CT).

Methods:
A total of 32 consecutive patients with available PCD-CT and EID-CT HRCT scans were included in the final analysis. The CT dose index (CTDIvol) was extracted from patient dose reports. Qualitative image analysis comprised the lung parenchyma and mediastinal structures and was assessed by 3 readers using a 5-point Likert scale. Quantitative image analysis included assessment of noise and signal-to-noise ratio in the lung parenchyma, trachea, aorta, muscle, and background.

Results:
The mean CTDIvol was 2.0 times higher in the conventional EID-CT scans (1.8±0.5 mGy) compared with PCD-CT (0.9±0.5 mGy, P<0.001). The overall image quality was rated significantly better by all 3 raters (P<0.001) in the PCD-CT relative to the EID-CT. Quantitative analysis showed no significant differences in noise and signal-to-noise ratio in the lung parenchyma between PCD-CT and EID-CT.

Conclusion:
Compared with conventional EID-CT scans, PCD-CT demonstrated similar or better objective and subjective image quality at significantly reduced dose levels in an intrapatient comparison. These results and their effect on clinical decision-making should be further investigated in prospective studies.
Increased maternal non-oxidative energy metabolism mediates association between prenatal DEHP exposure and offspring ASD symptoms: a birth cohort study
Authors: Thomson Sarah , Drummond Katherine , O’Hely Martin , Symeonides Christos , Chandran Chitra , Mansell Toby , Saffery Richard , Sly Peter , Vuillermin Peter , Ponsonby Anne-Louise ,   the Barwon Infant Study Investigator Group
Published: June 2022

AbstractPrenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study, a population-based birth cohort of 1074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord blood at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) associations between higher prenatal di(2-ethylhexyl) phthalate (DEHP) levels and increased activity in maternal non-oxidative energy metabolism pathways, specifically non-oxidative pyruvate metabolism and the Warburg Effect, and (ii) associations between increased activity in these pathways and increased offspring ASD symptomology at 2 and 4 years of age. Mediation analyses suggested that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. Interventions targeting maternal metabolic activity in pregnancy may be beneficial in reducing the potential risk to the developing fetus.
Genome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture
Authors:   International League Against Epilepsy Consortium on Complex Epilepsies, Berkovic Samuel F , Cavalleri Gianpiero L , Koeleman Bobby PC 
Published: June 2022

AbstractEpilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here, we report a trans-ethnic GWAS including 29,944 cases, stratified into three broad- and seven sub-types of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants substantially close the missing heritability gap for GGE. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analysis of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current anti-seizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.
Effect of HIV disease and the associated moderators on COVID-19 Mortality
Authors: Muthuka K. John , Muchiri W. Francis , Oluoch J. Kelly , Muchiri W. Francis , Nzioki M. Japheth 
Published: June 2022

AbstractIntroductionEstablished predictors for COVID 19 related mortalities are diverse. The impact of these several risk factors on coronavirus mortality have been previously reported in several meta-analyses limited by small sample sizes and premature data. The objective of this systematic review and meta-analysis coupled with meta-regression was to evaluate the updated evidence on the risk of COVID 19 related mortality by HIV serostatus using published data, and account for possible moderators.MethodElectronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID 19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty-two studies with a total of 19,783,097 patients detailing COVID 19 related mortality were included. To pool the estimate, a random effects model with risk ratio as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register.ResultsThe findings were consistent in stating the contribution of HIV infection for COVID-19 related mortality. The cumulative COVID-19 related mortality was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related mortality [RR=1.19, 95% CI (1.02, 1.39) (P=0.00001)] with substantial heterogeneity (I squared > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22. Multiple Centre studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092, 1.559) (P = 0.003)], similar to studies conducted in America (RR=1.422, 95% CI 1.233, 1.639) and South Africa (RR=202;1.123, 95% CI 1.052, 1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I squared = 0%)] and mechanical ventilation [(P=0.04) (I squared = 0%)] which are predictors of COVID-19 severity prior to death. Furthermore, risk of COVID 19 related mortality is influenced by the region of study (R squared = 0.60). The variance proportion explained by covariates was significant (I squared = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R squared = 0.67).ConclusionOur updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID 19 mortality, which might be modulated by the regions. We believe the updated data further will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)
Cognitive features of amnestic Mild Cognitive Impairment using specific Cambridge Neuropsychological Test Automated Battery test scores
Authors: Tran-Chi Vinh-Long , Amrapala Arisara , Nantachai Gallayaporn , Hemrungrojn Solaphat , Tunvirachaisakul Chavit , Maes Michael 
Published: June 2022

AbstractBackgroundIn older adults with amnestic Mild Cognitive Impairment (aMCI), the Cambridge Neuropsychological Test Automated Battery (CANTAB) probes indicated cognitive impairments most frequently in memory.ObjectivesThis study aimed to investigate a) the cognitive features of aMCI using memory CANTAB tests and b) whether the clinical diagnosis of aMCI can be externally validated by these CANTAB measurements.MethodsWe tested CANTAB tests that are specific to aMCI on 65 healthy controls and 66 people with aMCI who were diagnosed using Petersen’s criteria. These tests were spatial working memory (SWM), visual pattern recognition memory (PRM), delayed matching to sample (DSM), spatial span (SSP), and rapid visual information processing (RVP).ResultsThe key aMCI features are impairments in PRM and DSM, whilst deficits in SSP and RVP are other, albeit somewhat less important features of aMCI. Nevertheless, neural network analyses including 10 CANTAB domains specific for MCI showed that only 70.8 percent of all subjects were properly identified with a sensitivity of 77.3%, specificity of 65.4% and an area under the ROC curve of 0.760. K-means cluster analysis using the same specific CANTAB test scores discovered 2 clusters with an adequate silhouette measure of cohesion and separation including a cluster with 36 subjects showing impairments in most neurocognitive tests.ConclusionDeficits in spatial working, pattern recognition and visuospatial working memory as well as rapid visual information processing are key features of aMCI. Nevertheless, the clinical diagnosis of aMCI according to Petersen’s criteria is overinclusive because too many healthy controls are allocated to this group.