bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of cataract surgery in patients previously treated with orbital radiotherapy
Authors: Hind Jennifer , Jamison Aaron , Schipani Stefano , Connolly Julie , Cauchi Paul , Chadha Vikas 
Published: June 2021

Purpose:
To quantify the risks for cataract surgery in patients who have previously undergone external beam radiotherapy (EBRT).

Setting:
Tertiary ophthalmology and oncology hospital.

Design:
Retrospective case series.

Methods:
Patients treated with orbital EBRT at the Beatson West of Scotland Cancer Centre between 2001 and 2019 were identified, and clinical records were reviewed to identify those who had subsequently undergone cataract surgery. Preoperative and postoperative case records, and operation records, were reviewed to identify demographic data and data regarding complications and surgical outcomes.

Results:
46 eyes (of 33 patients) were included. The indications for EBRT included thyroid eye disease, lymphoma, choroidal metastases, and other orbital malignancies. Mean corrected preoperative Snellen visual acuity was 20/100 (range 20/30 to 20/2000) improving to 20/25 (20/12 to 20/160, 1-way analysis of variance P < .01). Mean visual gain was 0.5 logMAR (−0.9 to 1.9). There was 1 case of posterior capsule (PC) rupture with vitreous loss (2%). Dense PC plaque was noted intraoperatively in 19.5% (n = 9). 13% (n = 6) required Nd:YAG laser posterior capsulotomy. There were 6 cases (13%) of cystoid macular edema (CME).

Conclusions:
Visual outcomes after cataract surgery in this cohort of patients were similar to those obtained in a nationwide cohort. EBRT seemed to be associated with an increased incidence of intraoperative PC plaque, postoperative CME (which in most cases settled with treatment), and need for posterior capsulotomy.
The Physiologic and Emotional Effects of 360-Degree Video Simulation on Head-Mounted Display Versus In-Person Simulation
Authors: Caruso Thomas J. , Armstrong-Carter Emma , Rama Asheen , Neiman Nicole , Taylor Katherine , Madill Martine , Lawrence Kiley , Hemphill Sydney F. , Guo Nan , Domingue Benjamin W. 
Published: June 2021

Introduction
A key simulation component is its capability to elicit physiological changes, improving recall. The primary aim was to determine whether parasympathetic responses to head-mounted display simulations (HMDs) were noninferior to in-person simulations. The secondary aims explored sympathetic and affective responses and learning effectiveness.

Methods
The authors conducted a noninferiority trial. Hospital providers who did not use chronotropic medications, have motion sickness, or have seizures were included. The authors randomized participants to in-person or HMD simulation. Biometric sensors collected respiratory sinus arrhythmia and skin conductance levels to measure parasympathetic and sympathetic states at baseline, during, and after the simulation. Affect was measured using a schedule. The authors measured 3-month recall of learning points and used split-plot analysis of variance and Mann-Whitney U tests to analyze.

Results
One hundred fifteen participants qualified, and the authors analyzed 56 in each group. Both groups experienced a significant change in mean respiratory sinus arrhythmia from baseline to during and from during to afterward. The difference of change between the groups from baseline to during was 0.134 (95% confidence interval = 0.142 to 0.410, P = 0.339). The difference of change from during the simulation to after was −0.060 (95% confidence interval = −0.337 to 0.217, P = 0.670). Noninferiority was not established for either period. Sympathetic arousal did not occur in either group. Noninferiority was not established for the changes in affect that were demonstrated. The mean scores of teaching effectiveness and achievement scores were not different.

Conclusions
Although a parasympathetic and affective response to the video simulation on an HMD did occur, it was not discernibly noninferior to in-person in this study.
IMPPACT (Intravenous Monotherapy for Postoperative Perforated Appendicitis in Children Trial)
Authors: Lee Justin , Garvey Erin M. , Bundrant Nikkida , Hargis-villanueva Angela , Kang Paul , Osuchukwu Obiyo , Dekonenko Charlene , Svetanoff Wendy Jo , St. Peter Shawn D. , Padilla Benjamin , Ostlie Daniel 
Published: June 2021

Background:
Perforated appendicitis is the most common cause of intraabdominal abscess (IAA) in children. The optimal postoperative antibiotic regimen to reduce IAA has evolved in the last decade from triple-drug to 2-drug therapy (CM). Recent retrospective studies show decreased infectious complications with monotherapy PT. To date prospective comparative data are lacking. Therefore, a prospective randomized trial comparing PT versus CM was conducted.

Methods:
A multi-institutional prospective randomized trial was performed in children with perforated appendicitis comparing postoperative antibiotic regimens PT or CM. The primary outcome was 30-day postoperative IAA formation. Perforation was strictly defined as a hole in the appendix or fecalith in the abdomen, documented with intraoperative photographs.

Results:
One hundred sixty-two patients were enrolled during the study period. No differences in age, weight, or duration of presenting symptoms were identified. In addition, length of stay, duration of intravenous antibiotic treatment, discharge oral antibiotic treatment, and antibiotic-related complications did not differ between groups. Compared to the CM group, the PT group had significantly lower IAA rate [6.1% vs 23.8%, odd ratio (OR) 4.80, P = 0.002], lower postoperative computed tomography imaging rate (13.9% vs 29.3%, OR 2.57, P = 0.030), and fewer emergency room visits (8.8% vs 26.4%, OR 3.73, P = 0.022). Multivariate logistic regression analysis found the use of CM versus PT (OR 9.21, P = 0.021) to be the most significant predictor for developing IAA.

Conclusions:
In children with perforated appendicitis, postoperative monotherapy with PT is superior to standard 2-drug therapy with CM and does not increase antibiotic-related complications or antibiotic exposure duration.
SARS-CoV-2 in wastewater from Mexico City used for irrigation in the Mezquital Valley: quantification and modelling of geographic dispersion
Authors: Coronado Yaxk’in , Navarro Roberto , Mosqueda Carlos , Valenzuela Valeria , Perez Juan Pablo , González-Mendoza Víctor , de la Torre Mayra , Rocha Jorge 
Published: June 2021

AbstractQuantification of SARS-CoV-2 in urban wastewaters has emerged as a cheap, efficient strategy to follow trends of active COVID-19 cases in populations. Moreover, mathematical models have been developed that allow prediction of active cases following the temporal patterns of viral loads in wastewaters. In Mexico, no systematic efforts have been reported in the use of this strategies. In this work, we quantified SARS-CoV-2 in rivers and irrigation canals in the Mezquital Valley, Hidalgo, an agricultural region where wastewater from Mexico City is distributed and used for irrigation. Using quantitative RT-PCR, we detected the virus in 6 out of 8 water samples from rivers, and 5 out of 8 water samples from irrigation canals. Notably, samples showed a general consistent trend of having the highest viral loads in the sites closer to Mexico City, indicating that this is the main source that contributes to detection. Using the data for SARS-CoV-2 concentration in the river samples, we generated a simplified transport model that describes the spatial patterns of dispersion of virus in the river. We suggest that this model can be extrapolated to other wastewater systems that require knowledge of spatial patterns of viral dispersion at a geographic scale. Our work highlights the need for improved practices and policies related to the use of wastewater for irrigation in Mexico and other countries.
“You’re too young to have an eye problem”: Reasons for nonadherence to referrals for follow-up eye care for schoolchildren in Nigeria -- a descriptive qualitative study
Authors: Lohfeld Lynne , Graham Christine , Ebri Anne Effiom , Congdon Nathan , Chan Ving Fai 
Published: June 2021

AbstractStudy objectivesto identify reasons for non-adherence to referrals for follow-up eye care after children fail a school vision screening test.MethodsTen focus groups were held with parents or guardians (‘parents’) of children who had not adhered to the referral for further care in Cross River State, Nigeria, in 2019. Data from verbatim transcripts were analysed deductively using topics from the interview guide plus ‘Other’ to capture unanticipated results. Analysts followed procedures for Qualitative Content Analysis plus a modified Framework Method to identify overarching themes and barriers that are both highly salient (most frequently mentioned) and relevant (discussed in at least half of all groups).ResultsThree themes identified in the data are 1) modifiable barriers (key among them being parental beliefs and problems with the referral letter), 2) contextual factors (parents’ situation, attitudes towards children and beliefs about care) and 3) participants’ recommendations to improve the child eye care program (educate the general public and correct parents’ misconceptions). Many of the findings echoed those from previous studies conducted in both low-and-middle income countries (LMICs) and high-income countries (HICs).ConclusionThis study went beyond identifying modifiable barriers to also identify contextual factors and what parents recommend be done to improve vision care for children in Cross River State, Nigeria. If acted on, these findings may increase acceptance and uptake of eye care services that can promote sustainability and spread of the program to other parts of Nigeria and/or Africa.
Multi-omic landscaping of human midbrains identifies neuroinflammation as major disease mechanism in advanced-stage Parkinson’s disease
Authors: Gomes Lucas Caldi , Galhoz Ana , Jain Gaurav , Roser Anna-Elisa , Maass Fabian , Carboni Eleonora , Barski Elisabeth , Lenz Christof , Lohmann Katja , Klein Christine , Bähr Mathias , Fischer André , Menden Michael P. , Lingor Paul 
Published: June 2021

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disorder whose prevalence is rapidly increasing worldwide. The disease mechanisms of sporadic PD are not yet completely understood. Therefore, causative therapies are still lacking. To obtain a more integrative view of disease-mediated alterations, we investigated the molecular landscape of PD in human post-mortem midbrains. Tissue from 13 PD patients and 10 controls was subjected to small RNA sequencing, transcriptomics, and proteomics analysis. Differential expression analyses were performed reveal multiple deregulated molecular targets linked to known pathomechanisms of PD as well as novel processes. We found significant differential expression of miR-539-3p, miR-376a-5p, miR-218-5p, and miR-369-3p, the valid miRNA-mRNA interacting pairs of miR-218-5p/RAB6C, and miR-369-3p/GTF2H3, as well as multiple proteins relevant in the pathology of PD, including CHI3L1, SELENBP1, PRDX1, HSPA1B, and TH. Vertical integration of multiple omics analyses allowed to validate disease-mediated molecular alterations across different molecular layers and functional annotation of differentially expressed targets identified a strong enrichment of pathways related to inflammation and activation of the immune response. This suggests that neuroinflammation may significantly contribute to disease progression in PD and may be a promising therapeutic target in advanced stages of PD.
The St. Gallen 2019 Guidelines understages the Axilla in Lobular Breast Cancer – a Population-Based Study
Authors: Narbe Ulrik , Bendahl Pär-Ola , Fernö Mårten , Ingvar Christian , Dihge Looket , Rydén Lisa 
Published: June 2021

AbstractBackgroundThe St. Gallen 2019 guidelines recommend omission of completion axillary lymph node dissection (cALND) in breast cancer patients with 1-2 sentinel lymph node (SLN) metastases regardless of histopathology. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with ≥4 axillary lymph node (ALN) metastases. We aimed to estimate the proportion of patients with invasive lobular cancer (ILC) and invasive ductal cancer of no special type (NST) and 1-2 SLN metastases for whom cALND would indicate need of adjuvant chemotherapy.MethodsPatients with ILC and NST histopathology undergoing primary surgery 2014-2017 were identified in the Swedish National Quality Breast Cancer register. After exclusion of patients with incongruent or missing data, 1886 patients who fulfilled the St. Gallen 2019 criteria for cALND omission were included in the study cohort.ResultsPatients with ILC (n = 329) had a higher metastatic nodal burden and more often a luminal A-like subtype compared with NST patients (n = 1507). The prevalence of ≥ 4 ALN metastases was higher in ILC (31%) than in NST (15%), corresponding to an adjusted odds of 2.26 (95% CI 1.59-3.21). Luminal A-like breast cancers with ≥4 ALN metastases were overrepresented in ILC cases (52/281 (19%)) compared to NST cases (43/1299 (3%)), P<0.001.ConclusionsPatients with ILC more often had a luminal A-like breast cancer with ≥4 ALN metastases compared with NST patients. Abstaining cALND in patients with luminal A-like ILC with 1-2 SLN metastases warrants future attention as it risks nodal understaging and hence undertreatment in one-fifth of these patients.Source of fundingThe authors declare no conflicts of interest. The Skåne County Councils Research and Developmental Foundation, the Governmental Funding of Clinical Research within the National Health Service (ALF), the Swedish Cancer Society, the Erling Persson Family Foundation, Kronoberg County Council’s Research and Development Foundation, The Cancer Foundation Kronoberg, The Swedish Research Council and The Swedish Breast Cancer Association. The funding agencies had no role in study design or interpretation of data.Previous communicationPreliminary findings were published as part of Ulrik Narbe’s doctoral thesis.Trial registrationISRCTN registry: ISRCTN14341750
GWAS on Birth Year Infant Mortality Rates Provides New Evidence of Recent Natural Selection
Authors: Wu Yuchang , Furuya Shiro , Wang Zihang , Nobles Jenna E. , Fletcher Jason M. , Lu Qiongshi 
Published: June 2021

AbstractFollowing more than a century of phenotypic measurement of natural selection processes, much recent work explores relationships between molecular genetic measurements and realized fitness in the next generation. We take a novel approach to the study of contemporary selective pressure by examining which genetic variants are “sustained” in populations as mortality exposure declines. Specifically, we deploy a so-called “regional GWAS” that links the infant mortality rate (IMR) by place and year in the UK with common genetic variants among cohorts in the UK Biobank. These cohorts (born 1936-1970) saw a decline in IMR from above 65 per 1,000 to under 20 per 1,000, with substantial subnational variation and spikes alongside wartime exposures. Our results show several genome-wide significant loci, including LCT and TLR10/1/6, related to area-level cohort IMR exposure during gestation and infancy. Genetic correlations are found across multiple domains, including fertility, cognition, health behaviors, and health outcomes, suggesting an important role for cohort selection in modern populations.
CD56brightCD16- NATURAL KILLER CELLS ARE IN HIGHER COUNTS IN THE UMBILICAL CORD BLOOD THAN IN THE PERIPHERAL BLOOD
Authors: de Molla Vinicius Campos , Rodrigues Barbosa Míriam Cristina , Mendrone Alfredo , Gonçalves Matheus Vescovi , Kimura Eliza , Guirao Fabio , Yamamoto Mihoko , Arrais-Rodrigues Celso 
Published: June 2021

ABSTRACTUmbilical cord blood (UCB) is an alternative source for hematopoietic stem cells allogeneic hematopoietic stem cell transplantation in the absence of compatible donor. UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD) but is associated with slower engraftment and slower immune reconstitution as compared to other sources. Dendritic cells (DC) and Natural Killer cells (NK) play a central role in the development of GVHD, the graft versus leukemia (GvL) effect, and in the control of infectious complications. We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DC, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. In the UCB samples, there were higher counts of CD56brightCD16-NK cells (median 0.024×109/L), as compared to the PB samples (0.012×109/L, P<0.0001), CD56dimCD16bright NK cells (median 0.446×109/L vs. 0.259×109/L for PB samples, P= 0.001), and plasmacytoid dendritic cells (pDC, median 0.008×109/L for UCB samples vs. 0.006×109/L for PB samples, P= 0.03). Moreover, non-classical monocytes counts were lower in UCB than in PB (median 0.024×109/L vs. 0.051 x109/L, respectively, P< 0.0001). In conclusion, there were higher counts of NK cells and pDC, and lower counts of non-classical monocytes in UCB than in PB from healthy individuals. These findings might explain the lower incidence and severity of chronic GVHD although maintaining the GVL effect in UCB transplants recipients as compared to other stem cell sources.HighlightsCD56brightCD16- NK cells are more frequent in UCB than in PB.Plasmacytoid dendritic cells are more frequent in UCB than in PB.Non-classical monocytes are more frequent in PB than in UCB.
Skill-level based examination of forearm muscle activation associated with efficient wrist and finger movements during typing
Authors: Ito Takanori , Matsumoto Yuka , Funakoshi Hayase , Yoshida Mio , Kanemura Naohiko , Kokubun Takanori 
Published: June 2021

AbstractThis study aims to elucidate the relationship between the wrist and finger movements and forearm muscle activation of people with different typing skills. It hypothesizes that skilled typists (STs) can move their wrist and finger joints faster than unskilled typists (UTs) can because they can efficiently use their muscles according to the activity characteristics of the flexors and extensors of the wrist joint. During the typing task, we measured wrist and finger movements using a 3D motion capture system and forearm muscle activation using surface electromyography. The angular velocity of the wrist and finger flexion/extension and the muscle activation of the wrist flexors was higher in the STs than that in the UTs while the muscle activation of the wrist extensors was higher in the latter than that in the former. Our results showed that STs may have used their forearm muscles to take advantage of the physical characteristics of the keys and the spring characteristics of their muscles and tendons. It was suggested that they placed less mechanical stress on their finger muscles and tendons when pressing and releasing the keys.
Cigarette Smoking-Associated Isoform Switching and 3’ UTR Lengthening Via Alternative Polyadenylation
Authors: Xu Zhonghui , Platig John , Lee Sool , Boueiz Adel , Chase Rob , Jain Dhawal , Gregory Andrew , Suryadevara Rahul , Berman Seth , Bowler Russell , Hersh Craig P. , Laederach Alain , Castaldi Peter J. ,   for the COPDGene Investigators
Published: June 2021

AbstractBackgroundCigarette smoking accounts for approximately one in five deaths in the United States. Previous genomic studies have primarily focused on gene level differential expression to identify related molecular signatures and pathways, but the genome-wide effects of smoking on alternative isoform regulation and posttranscriptional modulation have not yet been described.ResultsWe conducted RNA sequencing (RNA-seq) in whole-blood samples of 454 current and 767 former smokers in COPDGene Study. We assessed the association of current smoking with differential expression of genes and isoforms and differential usage of isoforms and exons. At 10% FDR, we detected 3,167 differentially expressed genes, 2,014 differentially expressed isoforms, 945 differentially used isoforms and 160 differentially used exons. Genes containing differentially used isoforms were enriched in biological pathways involving GTPase activity and innate immunity. The majority of these genes were not differentially expressed, thus not identifiable from conventional differential gene expression analysis. Isoform switch analysis revealed for the first time widespread 3′ UTR lengthening associated with cigarette smoking, where current smokers were found to have higher expression and usage of isoforms with markedly longer 3′ UTRs. The lengthening of 3′ UTRs appears to be mediated through alternative usage of distal polyadenylation sites, and these extended 3′ UTR regions are significantly enriched with functional sequence elements including adenylate-uridylate (AU)-rich elements, microRNA and RNA-protein binding sites. Expression quantitative trait locus analyses on differentially used 3′ UTRs identified 79 known GWAS variants associated with multiple smoking-related human diseases and traits.ConclusionsSmoking elicits widespread transcriptional and posttranscriptional alterations with disease implications. It induces alternative polyadenylation (APA) events resulting in a switch towards the usage of isoforms with strikingly longer 3′ UTRs in genes related to multiple biological pathways including GTPase activity and innate immunity. The extended 3′ UTR regions are enriched with functional sequence elements facilitating post-transcriptional regulation of protein expression and mRNA stability. These findings warrant further studies on APA events as potential biomarkers and novel therapeutic targets for smoking-related diseases.
Region-based analysis of rare genomic variants in whole-genome sequencing datasets reveal two novel Alzheimer’s disease-associated genes: DTNB and DLG2
Authors: Prokopenko Dmitry , Lee Sanghun , Hecker Julian , Mullin Kristina , Morgan Sarah , Katsumata Yuriko ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Weiner Michael W. , Fardo David W. , Laird Nan , Bertram Lars , Hide Winston , Lange Christoph , Tanzi Rudolph E. 
Published: June 2021

AbstractAlzheimer’s disease (AD) is a genetically complex disease for which roughly 30 genes have been identified via genome-wide association studies. We attempted to identify rare variants (minor allele frequency <0.01) associated with AD in a region-based, whole genome sequencing (WGS) association study (GSAS) of two independent AD family datasets (NIMH/NIA; 2247 individuals; 605 families). Employing a sliding window approach across the genome, we identified several regions that achieved p-values < 10−6, using the burden test or the SKAT statistic. The genomic region around the dystobrevin beta (DTNB) gene was identified with the burden test and replicated in case/control samples from the ADSP study (pmeta = 4.74×10−8). SKAT analysis revealed region-based association around the discs large homolog 2 (DLG2) gene and replicated in case/control samples from the ADSP study (pmeta =1×10−6). Here, in a region-based GSAS of AD we identified two novel AD genes, DLG2 and DTNB, based on association with rare variants.