bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Mutations of Canalicular Transporter Proteins Causing Low Phospholipid-Associated Cholelithiasis and Transient Neonatal Cholestasis in an Infant
Authors: Lourembam, Radhapyari , Malik, Rohan , Bolia Rishi
Published: April 2021

Low phospholipid-associated cholelithiasis syndrome is characterized by the development of cholelithiasis in early adulthood (<40 years of age) but is rarely diagnosed in childhood. It is associated with gene sequence variants in the ABCB4 gene encoding the multidrug resistance protein 3 which are mostly heterozygous. Transient neonatal cholestasis has been reported with heterozygous mutations in both ABCB4 and ABCB11 (Bile Salt Exporter Protein). We report a 3-month-old male with cholelithiasis and transient neonatal cholestasis in the setting of combined pathogenic heterozygous mutations in the genes ABCB4 and ABCB11. Initiation of ursodeoxycholic acid therapy led to a resolution of the cholestasis and gall stones. Our case highlights the complex nature of the genetics of cholestatic disorders.
In Search of Workforce Diversity? A Program’s Successful Approach
Authors: Llado-Farrulla Monica , Fosnot Joshua , Couto Javier , Chang Benjamin , Broach Robyn B. , Rios-Diaz Arturo , Fowler Jessica A. , Aarons Cary B. , Serletti Joseph M. , Butler Paris D.
Published: April 2021

The persistence of health care disparities along racial and ethnic lines highlights the complex and multifactorial nature of this national concern. The paucity of physicians ethnically underrepresented in medicine to treat an ever-growing heterogeneous population inherently contributes to these ongoing disparities. The authors proposed an approach to improve the representation of physicians underrepresented in medicine in their plastic surgery residency program. With a renewed commitment to ethnic diversity and inclusion, a multifaceted recruitment and retention approach was implemented at the University of Pennsylvania plastic and reconstructive surgery residency program from 2015 to 2020 (5 academic years). A retrospective review of the demographics of the program’s residents was then assessed over the past 9 academic years for comparison (2011 to 2020). The representation of underrepresented-in-medicine residents within the plastic and reconstructive surgery residency program steadily increased with the implementation of this multifaceted approach, reaching an unprecedented high. Currently, 29 percent of all residents are underrepresented in medicine and 29 percent are female, some of whom are also underrepresented in medicine. Although the female representation is on par with the national average, the underrepresented-in-medicine representation is far greater than the national average. As a result of this multifaceted approach, the representation of African American and Latino plastic surgery residents at the University of Pennsylvania now far exceeds current national averages. Unfortunately, the representation of Native American and Alaskan Natives is still lacking, despite the program’s broadened recruitment efforts. The success of this experience describes a successful strategy that institutions can implement to enhance underrepresented-in-medicine representation among its plastic surgery trainees.
The Importance of Financial Metrics in Physician Funding and Performance Evaluation
Authors: Patrinely J. Randall , Walker Sallie H. , Glassman Gabriella E. , Davis Matthew J. , Abu-Ghname Amjed , Khan Umraz , Drolet Brian C. , Forte Antonio J. , Perdikis Galen
Published: April 2021

Background:

Financial key performance indicators are often used to evaluate performance. Understanding of key performance indicators can be crucial for career advancement and bargaining leverage in resource negotiations. This study aimed to identify the most important key performance indicators used in surgical funding requests and understand how to use these metrics in clinical practice.

Methods:

In two tertiary medical centers, funding requests for surgeon gap support (2019 to 2020) and equipment (2017 to 2019) within departments of surgery were reviewed. The requesting department, approval status, and amount allotted were recorded. In requests for gap support, projections for contribution margin, operating room volume, charges, collections, and relative value units were tracked. Projected contribution margin and cost savings were recorded for equipment funding requests.

Results:

There were 40 gap support and 24 equipment requests, and all were approved. Most gap support requests included collections (90.0 percent), charges (87.5 percent), operating room cases (80.0 percent), relative value units (77.5 percent), and hospital contribution margin (77.5 percent). The most represented departments were general surgery (37.5 percent), neurosurgery (22.5 percent), and plastic surgery (15.0 percent). The departments that submitted the most equipment requests were general surgery (28.0 percent) and neurosurgery (28.0 percent). Most requests included projections for contribution margin (95.8 percent) and cost savings (87.4 percent). Projected hospital contribution margin correlated with the amount of funds allotted for surgeon support (r = 0.409; p = 0.022).

Conclusions:

This multicenter study identified the importance of using key performance indicators for a successful financial outcome in funding requests. In addition, the authors demonstrate the need for surgeons to understand their own key performance indicators. Surgeons should advocate for increased transparency to better understand their financial contributions and performance.
Revision Breast Reconstruction with Prepectoral Pocket Conversion of Submuscular Breast Implants
Authors: Kraenzlin Franca , Chopra Karan , Kokosis George , Venturi Mark L. , Mesbahi Ali , Nahabedian Maurice Y.
Published: April 2021

Background:

Prepectoral reconstruction using prosthetic devices has demonstrated a notable increase in popularity and confers a number of advantages over subpectoral placement, including minimal animation, no pain secondary to muscle spasm, and less device displacement or malposition. As such, more women with implants in the dual-plane position are seeking a remedy for animation deformities, chronic pain caused by muscle spasm, and implant malposition. The purpose of this study was to review outcomes following the conversion from subpectoral to prepectoral implant placement.

Methods:

This was a retrospective review of 63 patients who underwent breast implant conversion from the subpectoral plane to the prepectoral plane from 2009 to 2019.

Results:

A total of 73 implant pocket conversions from subpectoral to prepectoral were performed on 41 women who met inclusion criteria for this study. The mean time interval from the initial subpectoral operation to the prepectoral conversion was 1608.4 days. The reasons cited for prepectoral conversion was animation deformity (87.8 percent), significant levels of pain related to the implant (34.1 percent), capsular contracture (26.8 percent), or asymmetries and implant displacements (9.8 percent); 7.8 percent of individuals continued to experience their presenting symptom after plane conversion. Rippling and wrinkling were noted in 19.5 percent of individuals and edge visibility was documented in 4.9 percent. Complication rates were low, and no patients experienced necrosis of the mastectomy flap or nipple-areola complex.

Conclusions:

The use of prepectoral conversion for revision implant-based breast reconstruction successfully resolves animation deformity. This technique can be reliably and safely performed in a variety of patient demographics.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Early Diagnosis of HIV-1 and HIV-2 Using Cobas HIV-1/HIV-2 Qualitative Test: A Novel Qualitative Nucleic Acid Amplification Test for Plasma, Serum, and Dried Blood Spot Specimens
Authors: Hans Lucia , Allmen Nicole von , Edelmann Anke , Hofmann Jörg , Nilsson Alex Y. , Simon Christian O. , Seiverth Britta , Gohl Peter , Carmona Sergio
Published: April 2021

Background:

Nucleic acid amplification tests (NATs) minimize the time from HIV infection to diagnosis, reducing transmission during acute HIV. NATs are especially useful for diagnosing HIV in children younger than 18 months and discriminating between HIV-1 and HIV-2.

Methods:

We evaluated the performance of the cobas HIV-1/HIV-2 qualitative (cobas HIV-1/2 Qual) test for use on cobas 6800/8800 Systems. The results of adult plasma and serum samples and pediatric dried blood spots were compared with those of the recomLine HIV-1 & HIV-2 Immunoglobulin G serological test and COBAS AmpliPrep/COBAS TaqMan HIV-1 qualitative test, v2.0. Genotype inclusivity and limits of detection were determined, and sensitivity on seroconversion panels was compared with that in the Bio-Rad Geenius HIV 1/2 Confirmatory Assay, Abbott ARCHITECT HIV Ag/Ab Combo serological test, and cobas TaqScreen MPX, v2.0.

Results:

Concordance of cobas HIV-1/2 Qual test with the comparator serological test and COBAS AmpliPrep/COBAS TaqMan test was ≥99.6% with all sample types. Reactivity with all HIV genotypes was 100%. LOD in plasma samples was 14.8, 12.6, and 27.9 copies/mL for HIV-1 group M, HIV-1 group O, and HIV-2, respectively, with similar results for serum samples. LOD in dried blood spots was 255 copies/mL for HIV-1 and 984 copies/mL for HIV-2. HIV infection was detected 18.9 days and 8.5 days earlier than the confirmatory and serological assays, respectively, and at a similar time to the NAT.

Conclusions:

The cobas HIV-1/2 Qual test enables early and accurate diagnoses of HIV-1 and HIV-2 in adults and children across sample types. The assay could help avert transmission during acute HIV, simplify HIV diagnostic algorithms, and promote the survival of HIV-infected children.
Addressing Racial Disparities in Live Donor Kidney Transplantation Through Education and Advocacy Training
Authors: King Elizabeth A. , Ruck Jessica M. , Garonzik-Wang Jacqueline , Bowring Mary G. , Kumar Komal , Purnell Tanjala , Cameron Andrew , Segev Dorry L.
Published: April 2021

Background.

The Live Donor Champion (LDC) program trains kidney transplant (KT) candidates and their family/friends (“champions”) as educator-advocates for live donor KT (LDKT). This program was created to empower patients and champions, particularly African American (AA) waitlist candidates that historically had lower access to LDKT. We assessed changes in knowledge about and comfort discussing live donation and donor referral associated with LDC participation, both overall and by participant race.

Methods.

We compared 163 adult KT candidates who were LDC participants from October 2013 to May 2016 with 489 matched controls, both overall and by race. We compared changes in comfort and knowledge post-LDC using rank-sum tests among participants by race. We compared time to first live donor referral for participants versus controls, by race, using Cox regression.

Results.

Post-LDC versus pre-LDC, participants had higher median knowledge (83% versus 63% on 12-question quiz; P < 0.001) and comfort (1.8 versus 1 on 4-point Likert scale; P < 0.001). Among participants, AAs had similar baseline and final knowledge (P = 0.9 and P = 0.1, respectively) and baseline comfort (P > 0.9) as non-AAs but higher final comfort (2 versus 1.4; P = 0.005) than non-AAs. LDC participants were 5.8 times as likely as controls to have a live donor referral (aHR 3.765.788.89; P < 0.001); the impact of LDC participation was similar among non-AAs and AAs (p-interaction = 0.6).

Conclusions.

The LDC program increased knowledge, comfort, and live donor referral for non-AA and AA participants, underscoring the effectiveness in the program in promoting LDKT in a population with historically lower access to LDKT.
Guaico Culex virus NSP2 has RNA helicase and chaperoning activities
Authors: Zhang Xue-Yi , Shu Ting , Wang Xiaotong , Xu Jiuyue , Qiu Yang , Zhou Xi
Published: April 2021

RNA-remodelling proteins, including RNA helicases and chaperones, function to remodel structured RNAs and/or RNA–protein interactions and play indispensable roles in viral life cycles. Guaico Culex virus (GCXV) is the first uncovered animal-infected multicomponent virus with segmented positive-sense genomic RNAs. GCXV belongs to the Jingmenvirus group, a diverse clade of segmented viruses that are related to the prototypically unsegmented Flavivirus. However, little is known about the exact functions of the GCXV-encoded proteins. Here, we show that the putative non-structural protein (NSP) 2 on segment 2 of GCXV functions as an RNA helicase that unwinds RNA helix bidirectionally in an adenosine triphosphate (ATP)-dependent manner, and an RNA chaperone that remodels structured RNAs and facilitates RNA strand annealing independently of ATP. Together, our findings are the first demonstration of RNA-remodelling activity encoded by Jingmenvirus and highlight the functional significance of NSP2 in the GCXV life cycle.
Dynamics of neurotransmitter and extracellular vesicle-derived microRNA landscapes during heroin and methamphetamine withdrawal
Authors: Yu Juehua , Chen Fengrong , Xu Yu , Shi Kai , Zhang Zunyue , Peng Qingyan , Xie Zhenrong , Lu Jing , Wu Hongjin , Ma Yuru , Zou Lei , Zhou Yong , Chen Cheng , Yang Jiqing , Kuang Yiqun , Wang Yuan , Tan Tao , Zhu Mei , Robbins Trevor W. , Wang Kunhua
Published: April 2021

Circulating miRNAs in small vesicles known as exosomes within blood have been emerging as a new research hotspot in the field of psychiatric disorders. The aim of this work was to characterize the changes in exosomal microRNA profiles, both short-term and long-term, during substance withdrawal using a cross-sectional study design. Using weighted gene co-expression network analysis, a series of known, conserved, and novel exosomal microRNAs were identified as being associated with withdrawal stage and key neurotransmitters GABA, choline, and serotonin. Bioinformatics analyses established that the differences in the miRNA profile target signaling pathways are associated with developmental and intellectual abnormalities. Notably, a set of dysregulated microRNA signatures including hsa-mia-451a and hsa-mir-21a resulted in an AUC of 0.966 and 0.861, respectively, for predicting patients with substance use disorders. Furthermore, hsa-miR-744a-5p was positively correlated with serotonin, and its important role in maintaining neuronal development and function was revealed using an in vitro human induced pluripotent stem cells derived neuronal model. Taken together, these data suggest that the microRNA content of circulating exosomes represent a biomolecular “fingerprint” of the progression of substance withdrawal and may uncover the putative mechanism of how these exosomal microRNAs contribute to central nervous system development and function.
Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health system
Authors: Pawlowski Colin , Rincón-Hekking John , Awasthi Samir , Pandey Viral , Lenehan Patrick , Venkatakrishnan AJ , Bade Sairam , O’Horo John C. , Virk Abinash , Swift Melanie D. , Williams Amy W. , Gores Gregory J. , Badley Andrew D. , Halamka John , Soundararajan Venky
Published: April 2021

Cerebral venous sinus thrombosis (CVST) has been reported in a small number of individuals who have received the mRNA vaccines1or the adenoviral vector vaccines for COVID-19 in the US2and Europe3. Continued pharmacovigilance is integral to mitigating the risk of rare adverse events that clinical trials are underpowered to detect, however, these anecdotal reports have led to the pause or withdrawal of some vaccines in many jurisdictions and exacerbated vaccine hesitancy at a critical moment in the fight against the COVID-19 pandemic. We investigated the frequencies of CVST seen among individuals who received FDA-authorized COVID-19 vaccines from Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses) and Johnson & Johnson - J&J (n = 1,745 doses), and among individuals receiving one of 10 FDA-approved non-COVID-19 vaccines (n = 771,805 doses). Comparing the incidence rates of CVST in 30-day time windows before and after vaccination, we found no statistically significant differences for the COVID-19 vaccines or any other vaccines studied in this population. In total, we observed 3 cases of CVST within the 30 days following Pfizer-BioNTech vaccination (2 females, 1 male; Ages (years): [79, 80, 84]), including one individual with a prior history of thrombosis and another individual with recent trauma in the past 30 days. We did not observe any cases of CVST among the patients receiving Moderna or J&J vaccines in this study population. We further found the baseline CVST incidence in the study population between 2017 and 2021 to be 45 to 98 per million patient years. Overall, this real-world evidence-based study highlights that CVST is rare and is not significantly associated with COVID-19 vaccination. In addition, there is a need for a concerted international effort to monitor EHR data across diverse patient populations and to investigate the underlying biological mechanisms leading to these rare clotting events.
Impact of COVID-19 restrictions on diabetes health checks and prescribing for people with type 2 diabetes: a UK-wide cohort study involving 618,161 people in primary care
Authors: Carr Matthew J. , Wright Alison K. , Leelarathna Lalantha , Thabit Hood , Milne Nicola , Kanumilli Naresh , Ashcroft Darren M. , Rutter Martin K.
Published: April 2021

OBJECTIVE

To compare rates of performing NICE-recommended health checks and prescribing in people with type 2 diabetes (T2D), before and after the first COVID-19 peak in March 2020, and to assess whether trends varied by age, sex and deprivation.

METHODS

We constructed a cohort of 618,161 people with T2D followed between March and December 2020 from 1744 UK general practices registered with the Clinical Practice Research Datalink (CPRD; Aurum and GOLD databases). We focused on the following six health checks and prescribing: HbA1c, serum creatinine, cholesterol, urinary albumin excretion, blood pressure and BMI assessment, comparing trends using regression models and 10-year historical data.

RESULTS

In April 2020, in English practices, rates of performing health checks were reduced by 76-88% when compared to 10-year historical trends, with older people from deprived areas experiencing the greatest reductions. Between May and December 2020, the reduced rates recovered gradually but overall remained 28% and 47% lower compared to historical trends, with similar findings in other UK nations. In England, rates of prescribing of new medication fell during April with reductions varying from 10% (4-16%) for antiplatelet agents to 60% (58-62%) for antidiabetic medications. Overall, between March and December 2020, the overall rate of prescribing new diabetes medications was reduced by 19% (15-22%) and new antihypertensive medication by 22% (18-26%). Similar trends were observed in other UK nations, except for a reduction in new lipid-lowering therapy prescribing March to December 2020 (reduction: 16% (10-21%)).

CONCLUSIONS

Over the coming months, healthcare services will need to manage this backlog of testing and prescribing. Effective communications should ensure that patients remain engaged with diabetes services, monitoring and opportunities for prescribing, and make use of home monitoring and remote consultations.
Verification of the Abbott Alinity m Resp-4-Plex Assay for detection of SARS-CoV-2, influenza A/B, and respiratory syncytial virus
Authors: Cheng Annie , Riedel Stefan , Arnaout Ramy , Kirby James E.
Published: April 2021

COVID-19 symptomology may overlap with other circulating respiratory viruses that may also cause severe disease and for which there are specific and potentially life-saving treatments. The Abbott Alinity m Resp-4-Plex assay is a multiplex PCR assay that simultaneously detects and differentiates infection with SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV). We characterized its accuracy, precision, and analytical sensitivity. All were found to be robust for measures examined. In the context of sample-to-answer, near random access automation on the Alinity m platform, we believe that the Resp-4-Plex assay offers significant utility in addressing the current needs of the SARS-CoV-2 pandemic and future needs during anticipated endemic circulation of SARS-CoV-2 with other respiratory viruses.
Evaluation of a novel, rapid antigen detection test for the diagnosis of SARS-CoV-2
Authors: Thell Rainer , Kallab Verena , Weinhappel Wolfgang , Mueckstein Wolfgang , Heschl Lukas , Heschl Martina , Korsatko Stefan , Toedling Franz , Blaschke Amelie , Herzog Theresa , Klicpera Anna , Koeller Clara , Haugk Moritz , Kreil Anna , Spiel Alexander , Kreuzer Philipp , Krause Robert , Sebesta Christian , Winkler Stefan , Laky Brenda , Szell Marton
Published: April 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is currently finally determined in laboratory settings by real-time reverse-transcription polymerase-chain-reaction (rt-PCR). However, simple testing with immediately available results are crucial to gain control over COVID-19. The aim was to evaluate such a point-of-care antigen rapid test (AG-rt) device in its performance compared to laboratory-based rt-PCR testing in COVID-19 suspected, symptomatic patients.

Methods

For this prospective study, two specimens each of 541 symptomatic female (54.7%) and male (45.3%) patients aged between 18 and 95 years tested at five emergency departments (ED, n=296) and four primary healthcare centres (PHC, n=245), were compared, using AG-rt (positive/negative/invalid) and rt-PCR (positive/negative and cycle threshold, Ct) to diagnose SARS-CoV-2. Diagnostic accuracy, sensitivity, specificity, positive predictive values (PPV), negative predictive value (NPV), and likelihood ratios (LR+/-) of the AG-rt were assessed.

Results

Differences between ED and PHC were detected regarding gender, age, symptoms, disease prevalence, and diagnostic performance. Overall, 174 (32.2%) were tested positive on AG-rt and 213 (39.4%) on rt-PCR. AG correctly classified 91.7% of all rt-PCR positive cases with a sensitivity of 80.3%, specificity of 99.1%, PPV of 98.3, NPV of 88.6%, LR(+) of 87.8, and LR(-) of 0.20. The highest sensitivities and specificities of AG-rt were detected in PHC (sensitivity: 84.4%, specificity: 100.0%), when using Ct of 30 as cut-off (sensitivity: 92.5%, specificity: 97.8%), and when symptom onset was within the first three days (sensitivity: 82.9%, specificity: 99.6%).

Conclusions

The highest sensitivity was detected with a high viral load. Our findings suggest that AG-rt are comparable to rt-PCR to diagnose SARS-CoV-2 in COVID-19 suspected symptomatic patients presenting both at emergency departments and primary health care centres.

The rapid SARS-Cov-2 antigen test (SARS-CoV-2 Rapid Antigen Test (Roche Diagnostics), was compared in symptomatic patients with PCR testing both in emergency departments and primary health care centres. It showed an overall sensitivity of 80.3% and specificity of 99.1%; these were higher with lower PCR cycle threshold numbers and with a shorter onset of symptoms.
Impact of vaccination on new SARS-CoV-2 infections in the UK
Authors: Pritchard Emma , Matthews Philippa C. , Stoesser Nicole , Eyre David W. , Gethings Owen , Vihta Karina-Doris , Jones Joel , House Thomas , VanSteenHouse Harper , Bell Iain , Bell John I , Newton John N , Farrar Jeremy , Diamond Ian , Rourke Emma , Studley Ruth , Crook Derrick , Peto Tim , Walker A. Sarah , Pouwels Koen B.
Published: April 2021

The effectiveness of COVID-19 vaccination in preventing new SARS-CoV-2 infections in the general community is still unclear. Here, we used the Office for National Statistics (ONS) COVID-19 Infection Survey, a large community-based survey of individuals living in randomly selected private households across the UK, to assess the effectiveness of BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (<30 versus ≥30) as a surrogate for viral load, and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 RT-PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 days after the first dose (61%, 95% CI 54 to 68% versus 66%, 95% CI 60 to 71%, respectively) with greater reductions observed after a second dose (79%, 95% CI 65 to 88% versus 80%, 95% CI 73 to 85%, respectively). Largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of difference between the BNT162b2 and ChAdOx1 vaccines.
Inclusion of environmentally themed search terms improves Elastic Net regression nowcasts of regional Lyme disease rates
Authors: Kontowicz Eric , Brown Grant , Torner Jim , Carrel Margaret , Baker Kelly , Petersen Christine A.
Published: April 2021

Lyme disease is the most widely reported vector-borne disease in the United States. 95% of human cases are reported in the Northeast and upper Midwest. Human cases typically occur in the spring and summer months when an infected nymphIxodidtick takes a blood meal. Current federal surveillance strategies report data on an annual basis, leading to nearly a year lag in national data reporting. These lags in reporting make it difficult for public health agencies to assess and plan for the current burden of Lyme disease. Implementation of a nowcasting model, using historical data to predict current trends, provides a means for public health agencies to evaluate current Lyme disease burden and make timely priority-based budgeting decisions. The objective of this study was to develop and compare the performance of nowcasting models using free data from Google Trends and Centers of Disease Control and Prevention surveillance reports for Lyme Disease. We developed two sets of elastic net models for five regions of the United States first using monthly proportional hit data from 21 disease symptoms and tick related terms and second using monthly proportional hit data from all terms identified via Google correlate plus 21 disease symptom and vector terms. Elastic net models using the larger term list were highly accurate (Root Mean Square Error: 0.74, Mean Absolute Error: 0.52, R2: 0.97) for four of the five regions of the United States. Including these more environmental terms improved accuracy 1.33-fold while reducing error 0.5-fold compared to predictions from models using disease symptom and vector terms alone. Models using Google data similar to this could help local and state public health agencies accurately monitor Lyme disease burden during times of reporting lag from federal public health reporting agencies.
Altered Cortical Activation Associated with Mirror Overflow Driven by Non-Dominant Hand Movement in Attention-Deficit/Hyperactivity Disorder
Authors: Luo Yu , Chen Christine , Adamek Jack H , Crocetti Deana , Mostofsky Stewart H , Ewen Joshua B
Published: April 2021

Mirror overflow is involuntary movement that accompanies unilateral voluntary movement on the opposite side of the body, and is commonly seen in Attention-Deficit/Hyperactivity Disorder (ADHD). Children with ADHD show asymmetry in mirror overflow between dominant and non-dominant hand, yet there are competing mechanistic accounts of why this occurs. Using EEG during a sequential, unimanual finger-tapping task, we found that children with ADHD exhibited significantly more mirror overflow than typically developing (TD) controls, especially during the tapping of the non-dominant hand. Furthermore, source-level EEG oscillation analysis revealed that children with ADHD showed decreased alpha (8-12 Hz) event-related desynchronization (ERD) compared with controls in both hemispheres, but only during tapping of the non-dominant hand. Moreover, only the ERD ipsilateral to the mirror overflow during non-dominant hand movement correlated with both magnitude of overflow movements and higher ADHD symptom severity (Conners ADHD Hyperactivity/Impulsiveness scale) in children with ADHD. TD controls did not show these relationships. Our findings suggest that EEG differences in finger-tapping in ADHD are related primarily to voluntary movement in the non-dominant hand. Our results are also consistent with the Ipsilateral Corticospinal Tract (CST) Hypothesis, which posits that the atypical persistence of mirror overflow in ADHD may originate in the sensorimotor areas ipsilateral to mirror overflow and be transmitted via non-decussating CST fibers.
Identification of genetic mutations related to invasion and metastasis of acral melanoma via whole‐exome sequencing
Authors: Lim Youngkyoung , Lee Dong‐Youn
Published: April 2021

Many studies have analyzed the genes related to melanoma. However, only a limited number of studies have been conducted to identify the genes that are involved in the invasion and metastasis of acral melanoma (AM). Here, we attempted to investigate the genetic mutations associated with invasion and metastasis of AM. We analyzed five multi‐regional samples of primary and metastatic AM and histologically normal tissue adjacent to the tumor (NAT) in two AM patients by whole‐exome sequencing (WES). We identified single nucleotide variations and small indels present in tissue samples but not in saliva. We compared the sequencing results of superficial and deep lesions and primary and metastatic lesions of AM. We identified significantly deleterious mutations (SDM) that are likely to be related to invasion and metastasis of AM, respectively. SDM such as SKA3, MAST4, CNNM1, KIAA1549L, and SLC26A10 were found only in the deep lesion, but not in the superficial lesion. SDM present only in the metastatic lesion were ANO1, CPEB1, EP300, INADL, MAP1B, MAP7D1, MARCH6, NETO1, PRKCE, SBK1, TNRC6A, USP13, WDR74, and ZNF827. In conclusion, we applied multi‐region WES to investigate possible pathogenic mutations related to invasion and metastasis in AM. Several genes including CNNM1, USP13, ZNF827, WDR74, CPEB1, and EP300 might be related to invasion and metastasis of AM. This study might facilitate the exploration of the evolutionary pathogenesis of advanced AM.
“I Wish Them Well, but I Dare Not Trust Them”: John Wesley's Anti‐Catholicism in Context
Authors: O'Brien Glen
Published: April 2021

This article explores John Wesley's relationship both to Ireland and to the Roman Catholic faith and argues that Wesley's reputation as a proto‐ecumenist needs to become more muted and less idealised. Many in Ireland drew the intellectual content of their grievances against British rule from the rhetoric of liberty employed to support the Americans. Wesley's opposition to the rebellion of the colonists, as well as his support for the Church of Ireland and the Protestant landed gentry weakened the appeal of his message to the Catholic Irish. Wesley's ministry among the Pietist diaspora communities in Ireland, shows that he preferred their form of piety to that of the Catholic population. Wesley's anti‐Catholic sentiment was in keeping with widely‐held fears about Catholicism as a threat to Protestant liberty, and is considered here in the context of the rising strength of the Irish Catholic population in England and corresponding Acts to grant them greater liberties from the late 1770s. Wesley's support for the Protestant Association and the false accusation that he was an instigator of the 1780 Gordon Riots, his numerous anti‐Catholic pamphlets, and his correspondence with the Irish Capuchin monk Arthur O'Leary bring together an outline of Wesley's approach to Roman Catholicism which he saw as both a false religion and a threat to Britain's role as a global Protestant power.
Serum VEGF‐A and VEGFR‐1 levels in patients with adult immunoglobulin A vasculitis
Authors: Yücel Çiğdem , Sertoğlu Erdim , Fırat Oğuz Esra , Hayran Yıldız , Omma Ahmet , Özgürtaş Taner
Published: April 2021

Aim

Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor‐A (VEGF‐A) and VEGF receptor‐1 (VEGFR‐1) levels in adult IgAV patients.

Method

Thirty‐seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as “remission” or “active” according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF‐A, VEGFR‐1 levels and VEGFR‐1/VEGF‐A ratio were evaluated in patient and control groups.

Results

Serum median VEGF‐A, VEGFR‐1 and VEGFR‐1/VEGF‐A ratios were significantly higher in the patient group when compared to controls (235.9 [155‐308.4] pg/mL vs. 78.8 [29.7‐210.3] pg/mL, 400 [277.2‐724.3] pg/mL vs. 31.5 [12.5‐214.4] pg/mL and 1.85 [0.57‐2.97] vs. 0.46 [0.38‐0.63] respectively, all P values <.001). VEGFR‐1 had the strongest predictive value with a cut‐off value of 0.6 with 75% sensitivity and 73% specificity (P < .001).

Conclusion

This study is the first report indicating elevated serum VEGF‐A, VEGFR‐1, and more importantly VEGFR‐1/VEGF‐A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR‐1 seems to be a more important indicator of the ongoing inflammation.
Persistent headache and low back pain after accidental dural puncture in the obstetric population: a prospective, observational, multicentre cohort study
Authors: Niraj G. , Mushambi M. , Gauthama P. , Patil A. , Kelkar A. , Hart E. , Nurmikko T. ,   the Accidental Dural Puncture Outcome Study Collaborative Group
Published: April 2021

Accidental dural puncture following epidural insertion can cause a post‐dural headache that is defined by the International Headache Society as self‐limiting. We aimed to confirm if accidental dural puncture could be associated with persistent headache and back pain when compared with matched control parturients. We performed a prospective multicentre cohort study evaluating the incidence of persistent headache following accidental dural puncture at nine UK obstetric units. Parturients who sustained an accidental dural puncture were matched with controls who had undergone an uneventful epidural insertion. Participants were followed‐up at six‐monthly intervals for 18 months. Primary outcome was the incidence of persistent headache at 18 months. Ninety parturients who had an accidental dural puncture were matched with 180 controls. The complete dataset for primary analysis was available for 256 (95%) participants. Incidence of persistent headache at 18 months was 58.4% (52/89) in the accidental puncture group and 17.4% (29/167) in the control group, odds ratio (95%CI) 18.4 (6.0–56.7), p < 0.001, after adjustment for past history of headache, Hospital Anxiety and Depression Scale (depression) and Hospital Anxiety and Depression Scale (anxiety) scores. Incidence of low back pain at 18 months was 48.3% (43/89) in the accidental puncture group and 17.4% (29/167) in the control group, odds ratio (95%CI) 4.14 (2.11–8.13), with adjustment. We have demonstrated that accidental dural puncture is associated with long‐term morbidity including persistent headache in parturients. This challenges the current definition of post‐dural puncture headache as a self‐limiting condition and raises possible clinical, financial and medicolegal consequences.
Pedicled vascularized versus non‐vascularized bone grafts in the treatment of scaphoid non‐union: a meta‐analysis of comparative studies
Authors: Zhang Hanyu , Gu Jiaxiang , Liu Hongjun , Yuan Chaoqun
Published: April 2021

Background

Whether pedicled vascularized bone grafts (PVBGs) are beneficial over non‐vascularized bone grafts (NVBGs) still remains controversial. The aim of this study was to compare the clinical results of PVBGs and NVBGs for the treatment of scaphoid non‐union.

Methods

We conducted a meta‐analysis of the published studies comparing outcomes of these two different surgical techniques for scaphoid non‐union. Outcomes of union rate, time to union, functional results and re‐operation rate were analysed.

Results

Seven studies including four randomized controlled studies and three retrospective comparative studies with 413 participants were identified fitting inclusion criteria. Meta‐analysis showed that (i) union rate in PVBG groups was 1.13 times of NVBG groups (P = 0.002); (ii) the PVBG groups reached bone union significantly earlier by 1.73 weeks (P < 0.01); (iii) there was no significant difference in functional results, including active range of motion, grip strength, Mayo Wrist Score and excellent and good rate (P > 0.05); and (iv) re‐operation rate was similar between the two groups (P = 0.65).

Conclusions

Although the PVBG technique attains higher union rate and earlier union, this radiological advantage does not bring any functional benefits. In addition, PVBGs are of greater technical difficulty and need more operation requirements. Hence, clinicians should be cautious in electing PVBGs for treating scaphoid non‐union.
Daily interventions and assessments: The effect of online self‐compassion meditation on psychological health
Authors: Li Yanjuan , Hu Yueqin , Yang Wanting , Wang Yuyin
Published: April 2021

Traditional self‐compassion‐based interventions have been shown to be beneficial for improving psychological health. With the development of technology, online interventions accessible via smart phones start to emerge. The current study aimed to use daily assessments to investigate the effect of online daily self‐compassion interventions and its improvement pattern. Sixty‐five employees were recruited and completed a 4‐week study. The first week was the control period; the second week and the third week were the intervention period and the fourth week was the follow‐up period. Online self‐compassion meditation significantly improved daily self‐compassion and reduced perceived stress and emotional exhaustion, with varied changing patterns. Daily self‐compassion and perceived stress did not change in the control period, then started to increase/decline with time during the intervention period, and remained stable in the follow‐up period. Daily emotional exhaustion declined with time in the control period and remained stable in the intervention and follow‐up period. The intervention effects did not differ for individuals with different levels of trait self‐compassion. This study shows that daily online self‐compassion meditation is effective and reveals how it works. Future studies can apply this method to examine the effectiveness of other daily online interventions.
Ethics of vaccination: Should capability measures be used to inform SARS‐CoV‐2 vaccination strategies?
Authors: Millar Michael R. , Gourtsoyannis Yannis , Jayakumar Angelina
Published: April 2021

Proposals for SARS‐CoV‐2 virus vaccination priorities in the UK and in many other countries are heavily influenced by epidemiological models, which use outcome measures such as deaths or hospitalisation. Limiting the values under consideration to those attributable to the direct effects of infection has the advantage of simplifying the models and the process of decision‐making. However, the consequences of the pandemic extend beyond outcomes directly attributable to SARS‐CoV‐2 infection, and include restrictions on educational and work opportunities, access to services, recreational activities, affiliations and relationships with others, freedom of movement (including escaping abusive relationships), and other determinants of human experience.

Capability theory gives emphasis to the freedoms that individuals have to express themselves (in doings and beings). Restrictions on freedoms restrict our capabilities. Capability theory has been used to provide a framework for the evaluation and comparison of international development approaches and in the evaluation of public health policy. There is a clustering of disadvantages associated with this pandemic that adds to pre‐existing inequalities. Much of the disadvantage engendered in the SARS‐CoV‐2 pandemic is left out when public health policy is based on a limited range of metrics. Acknowledging the impact of policy across the range of human freedoms at both a national and international level has the potential to improve policy, facilitate the mitigation of direct and indirect adverse consequences, and improve public confidence and the effectiveness of vaccine deployment strategies.
College Admission Tests and Social Responsibility
Authors: Koljatic Mladen , Silva Mónica , Sireci Stephen G.
Published: April 2021

In this article we address the mounting criticism and rejection of standardized tests used in the selection of students for college or university education. Admission tests are being increasingly demonized in many parts of the world and many colleges and universities are dropping tests for selection purposes, claiming the tests are detrimental to fair selection. The testing industry is at the center of this criticism and is accused of maintaining, and even facilitating, the social ills associated with admissions testing, much like iconic business corporations were accused of supporting unfair labor practices in the 1990s. The response of some business corporations to those criticisms was to embrace corporate social responsibility and increase transparency and accountability in their operations. Unfortunately, such acceptance of responsibility and increased transparency have not emerged in the testing industry. We believe the legitimacy of admission tests will continue to be challenged until the testing industry adopts a new way of conducting their business to regain the goodwill of relevant stakeholders in society that so far have been largely ignored.
Ultraearly thrombolysis by an anesthesiologist in a mobile stroke unit: A prospective, controlled intervention study
Authors: Larsen Karianne , Jæger Henriette S. , Tveit Lars H. , Hov Maren R. , Thorsen Kjetil , Røislien Jo , Solyga Volker , Lund Christian G. , Bache Kristi G.
Published: April 2021

Background

Acute stroke treatment in mobile stroke units (MSU) is feasible and reduces time‐to‐treatment, but the optimal staffing model is unknown. We wanted to explore if integrating thrombolysis of acute ischemic stroke (AIS) in an anesthesiologist‐based emergency medical services (EMS) reduces time‐to‐treatment and is safe.

Methods

A nonrandomized, prospective, controlled intervention study. Inclusion criteria: age ≥18 years, nonpregnant, stroke symptoms with onset ≤4 h. The MSU staffing is inspired by the Norwegian Helicopter Emergency Medical Services crew with an anesthesiologist, a paramedic‐nurse and a paramedic. Controls were included by conventional ambulances in the same catchment area. Primary outcome was onset‐to‐treatment time. Secondary outcomes were alarm‐to‐treatment time, thrombolytic rate and functional outcome. Safety outcomes were symptomatic intracranial hemorrhage and mortality.

Results

We included 440 patients. MSU median (IQR) onset‐to‐treatment time was 101 (71–155) minutes versus 118 (90–176) minutes in controls, p = 0.007. MSU median (IQR) alarm‐to‐treatment time was 53 (44–65) minutes versus 74 (63–95) minutes in controls, p < 0.001. Golden hour treatment was achieved in 15.2% of the MSU patients versus 3.7% in the controls, p = 0.005. The thrombolytic rate was higher in the MSU (81% vs 59%, p = 0.001). MSU patients were more often discharged home (adjusted OR [95% CI]: 2.36 [1.11–5.03]). There were no other significant differences in outcomes.

Conclusions

Integrating thrombolysis of AIS in the anesthesiologist‐based EMS reduces time‐to‐treatment without negatively affecting outcomes. An MSU based on the EMS enables prehospital assessment of acute stroke in addition to other medical and traumatic emergencies and may facilitate future implementation.
Ecumenism as Encounter
Authors: Binns John
Published: April 2021

This article is a personal testimony of the encounter between Orthodox and Anglican traditions in the 20th and the 21st centuries. It offers an overview of more than 40 years of experience in ecumenical work with Orthodox churches, beginning with an experience of Orthodoxy in Serbia in 1974 and a meeting with Fr Justin Popović. It continues with an account of the Fellowship of St Alban and St Sergius, which has enabled Anglicans to meet and worship with Orthodox. It concludes with a discussion of the ways in which these relationships matured after the fall of communism with the creation of the Institute for Orthodox Christian Studies in Cambridge as an example of shared theological education. The article also highlights how traditions from the East of spiritual fatherhood, the Jesus Prayer, and icons have become familiar parts of Anglican church life.
Senescent cell removal via JAG1‐NOTCH1 signalling in the epidermis
Authors: Yoshioka Hisashi , Yamada Takaaki , Hasegawa Seiji , Miyachi Katsuma , Ishii Yoshie , Hasebe Yuichi , Inoue Yu , Tanaka Hiroshi , Iwata Yohei , Arima Masaru , Sugiura Kazumitsu , Akamatsu Hirohiko
Published: April 2021

Emerging evidence has pointed to the noxious effects of senescent cells in various tissues, and senescent cells in the epidermis are known to accumulate with age. We hypothesized that there is a mechanism by which senescent cells in the epidermis are preferentially removed and that the function of such removal mechanism declines as age increases. In this study, we investigated whether Notch signalling is involved in such senescent cell removal. We found that Notch1 receptor was expressed more highly in p16INK4a‐positive senescent cells than in surrounding cells in human epidermis both in young and old subjects. On the other hand, the expression of its ligand JAG1 was decreased in the epidermis of aged subjects. When normal epidermal cells and UVB‐irradiated senescent cells were mixed and three‐dimensional reconstructed epidermis was developed in vitro, the senescent cells were preferentially removed from the basal layer and located in the upper layer. We also found that the depletion of senescent cells from the basal layer was suppressed by JAG1 knockdown in normal cells or using a Notch signalling inhibitor. From these results, Notch signalling may be involved in senescent cell removal in the epidermis and the age‐related decrease of JAG1 expression in the basal layer may lead to accumulation of senescent cells owing to reduced activation of Notch signalling.