bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of B-Cell-Depleted Patients With Coronavirus Disease 2019 Treated With Antispike Monoclonal Antibodies
Authors: Yetmar Zachary A , Khodadadi Ryan B , Seville Maria Teresa , Brumble Lisa , O’Horo John C , Ganesh Ravindra , Razonable Raymund R
Published: April 2022

Antispike monoclonal antibody treatment of 180 B-cell-depleted patients with mild-to-moderate coronavirus disease 2019 (COVID-19) resulted in good outcomes overall, with only 12.2% progressing to severe disease, 9.4% requiring hospitalization, 0.6% requiring mechanical ventilation, no deaths within 30 days, and 1.8% developing persistent COVID-19. Antispike monoclonal antibodies appear effective in this immunocompromised population.
Quaternary Collision-Zone Magmatism of the Greater Caucasus
Authors: Bewick Samuel , Parkinson Ian J , Harris Nigel , Adamia Shota , Sadradze Nino , Allen Mark B , Hammond Sam
Published: April 2022

The Greater Caucasus mountains (Cavcasioni) mark the northern margin of the Arabia–Eurasia collision zone. Magmatism in the central part of the Greater Caucasus began in the Pleistocene, up to ~25 Myr after initial collision. This paper presents bulk-rock and Sr–Nd–Pb isotope geochemistry from 39 Quaternary volcanic rock samples (<450 Ka) recovered from the Mt. Kazbek (Kasbegui) region of the Greater Caucasus, Georgia, to assess the sources and magmatic evolution of these lavas and the possible triggers for melting in the context of their regional tectonics. Compositions are dominantly calc-alkaline basaltic andesite to dacite (57–67 wt % SiO2). Although the lavas were erupted through thick continental crust, there is little evidence for extensive modification by crustal contamination. Trace element and isotopic systematics indicate that the lavas have supra-subduction zone signatures, most likely reflecting derivation from a lithospheric source that had been modified by melts and/or fluids from material subducted before and during the collisional event. Mass-balance modelling of the Sr–Nd isotope data indicates that the lavas require significant input from a subducted slab, with deep-sourced fluids fluxing the slab into the source region. In contrast with published data from Lesser Caucasus magmatism, data from the Mt. Kazbek region suggest that a compositionally distinct sediment source resides beneath the Greater Caucasus, producing characteristic trace element and Pb isotopic signatures. Two distinct compositional groups and therefore primary liquids can be discerned from the various volcanic centres, both derived from light rare-earth element enriched sources, but with distinct differences in Th/Yb and Dy/Yb ratios and Pb isotopes. Rare-earth element modelling of the lava sources is consistent with 3–4% melting starting in the garnet peridotite and continuing into the spinel facies or, potentially, sited in the garnet-spinel transition zone. Small-scale convection related to mantle upwelling provides a plausible mechanism for Greater Caucasus magmatism and explains the random aspect to the distribution of magmatism across the Arabia–Eurasia collision zone.
Price Discrimination by Negotiation: a Field Experiment in Retail Electricity
Authors: Byrne David P , Martin Leslie A , Nah Jia Sheen
Published: April 2022

We use a field experiment to study price discrimination in a market with price posting and negotiation. Motivated by concerns that low-income consumers do poorly in markets with privately negotiated prices, we built a call center staffed with actors armed with bargaining scripts to reveal negotiated prices and their determinants. Our actors implement sequential bargaining games under incomplete information in the field. By experimentally manipulating how information is revealed, we generate sequences of price offers that allow us to identify price discrimination in negotiations based on retailer perceptions of consumers’ search and switching costs. We also document differences in price distributions between entrants and incumbents, reflecting differences in captivity of their respective consumer bases. Finally, we show that higher prices paid by lower-income subsidy recipients in our market is not due to discriminatory targeting; they can be explained by variation in consumer willingness and ability to search and bargain.
Frequency of AA amyloidosis has decreased in Behçet’s syndrome: a retrospective study with long-term follow-up and a systematic review
Authors: Karatemiz Guzin , Esatoglu Sinem Nihal , Gurcan Mert , Ozguler Yesim , Yurdakul Sebahattin , Hamuryudan Vedat , Fresko Izzet , Melikoglu Melike , Seyahi Emire , Ugurlu Serdal , Ozdogan Huri , Yazici Hasan , Hatemi Gulen
Published: April 2022

Objective

A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA amyloidosis in our Behçet’s syndrome (BS) patients and to summarize the clinical characteristics of and outcomes for our patients, and also those identified by a systematic review.

Methods

We identified patients with amyloidosis in our BS cohort (as well as their clinical and laboratory features, treatment, and outcome) through a chart review. The primary end points were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered during 1976–2000 and those registered during 2001–2017, in order to determine whether there was any change in the frequency. We searched PubMed and EMBASE for reports on BS patients with AA amyloidosis. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.

Results

The prevalence of AA amyloidosis was 0.62% (24/3820) in the earlier cohort and declined to 0.054% (3/5590) in the recent cohort. The systematic review revealed 82 cases in 42 publications. The main features of patients were male predominance and a high frequency of vascular involvement. One-third of patients died within 6 months after diagnosis of amyloidosis.

Conclusion

The frequency of AA amyloidosis has decreased in patients with BS, which is similar to the decrease observed for AA amyloidosis due to other inflammatory and infectious causes. However, AA amyloidosis is a rare, but potentially fatal complication of BS.
Predicting Indian Supreme Court Judgments, Decisions, or Appeals
Authors: Sharma Sugam K , Shandilya Ritu , Sharma Swadesh
Published: April 2022

Legal predictive models are of enormous interest and value to legal community. The stakeholders, particularly, the judges and attorneys, can take the best advantages of these models to predict the case outcomes to further augment their future course of actions, for example speeding up decision making, support arguments, strengthening the defense, etc. However, accurately predicting the legal decisions and case outcomes is an arduous process, which involves several complex steps—finding suitable bulk case documents, data extracting, cleansing and engineering, etc. Additionally, the legal complexity further adds to its intricacies. In this paper, we introduce our newly developed Machine Learning (ML)-enabled legal prediction model and its operational prototype, eLegPredict, which successfully predicts the Indian supreme court decisions. The eLegPredict is trained and tested over 3072 supreme court cases and has achieved 76% accuracy (F1-score). The eLegPredict is equipped with a mechanism to aid end users, where as soon as a document with new case description is dropped into a designated directory, the system quickly reads through its content and generates prediction. To our understanding, eLegPredict is one of the first few legal prediction models trying to predict Indian supreme court decisions.
“I Was Facilitating Everybody Else’s Life. And Mine Had Just Ground to a Halt”: The COVID-19 Pandemic and its Impact on Women in the United Kingdom
Authors: Herten-Crabb Asha , Wenham Clare
Published: April 2022

A growing body of research has highlighted the disproportionately negative impact of the COVID-19 pandemic on women globally. This article contributes to this work by interrogating the lived realities of sixty-four women in the United Kingdom through semi-structured in-depth interviews, undertaken during the first and second periods of lockdown associated with COVID-19 in 2020. Categorizing the data by subgroup of women and then by theme, this article explores the normative and policy-imposed constraints experienced by women in 2020 with regard to paid and unpaid labor, mental health, access to healthcare services, and government representation and consideration of women. These findings highlight women’s varied and gendered experiences of the COVID-19 pandemic and emphasizes the role that government can proactively play in attending to gender inequalities throughout its COVID-19 response.
The Israeli private trust as an alternative to succession proceedings
Authors: Kaplan Alon , Liberman Meytal
Published: April 2022

How to use a trust as an alternative to a will to transfer assets to the next generation? This article will answer this question by first introducing the reader to inheritance and trust law in Israel. It will explore the endowment and how it should be used in order to regulate the transfer of assets to the next generation—how a trust should be set up and how assets should be transferred to it. The conclusion drawn from this analysis points out the key elements which should be considered when creating a trust to survive death under Israeli law.
Mental distress and health-related quality of life in gambiense human African trypanosomiasis: a case–control study in the Democratic Republic of Congo
Authors: Mudji Junior , Ackam Nancy , Amoako Yaw Ampem , Madinga Blaise , Mumbere Pépé , Agbanyo Abigail , Blum Johannes , Phillips Richard Odame , Molyneux David Hurst
Published: April 2022

Background

The extent to which neuropsychiatric sequelae affects the mental health status and quality of life of former gambiense human African trypanosomiasis (gHAT) patients is not known.

Methods

We assessed anxiety, depression and health-related quality of life (HRQoL) in 93 patients and their age- and sex-matched controls using the Hospital Anxiety and Depression Scale, Becks Depression Inventory and the 36-item Short Form Health Survey in structured interviews in the Vanga health zone in the Democratic Republic of Congo. Data were analysed using Stata version 14.0. The degree of association between neurologic sequelae and mental distress was evaluated using the Student's t-test and χ2 or Fisher's exact tests, where appropriate, with a p-value <0.05 deemed to be statistically significant.

Results

We found that neurological sequelae persisted in former patients at least 15 y after treatment. Depression (p<0.001) and anxiety (p=0.001) were significantly higher in former patients with neurologic sequelae. The mean quality-of-life (QoL) scores were significantly lower for patients than in controls in the physical, emotional and mental health domains.

Conclusions

The presence of neurological sequelae leads to mental distress and a diminished QoL in former gHAT patients. Minimising neurologic sequelae and incorporating psychosocial interventions should be essential management goals for gHAT.
It’s the Experience: A Course Redesign to Shift Student Perspectives on Population-Centered Nursing
Authors: Creed Joan M. , Cone April , Chappell Kate K. , Davis Victoria H.
Published: April 2022

An innovative experiential learning activity in an online undergraduate population health nursing course provided an authentic experience that connected course content with abstract concepts and patient situations. To address identified application needs, the design incorporated social determinants of health to enhance realism and applicability and build readiness for nursing practice through the experience.
Nursing First: Promoting Academic and Professional Success Through a Seamless Transition Program for Registered Nurses to Baccalaureate Students
Authors: Gambino Kathleen M. , Shaffer Cheryl , Ortiz Jennifer
Published: April 2022

The Nursing First Program was established to provide students in an associate of science in nursing program at a downstate New York community college a seamless transition into the registered nurse to baccalaureate program of a nearby university while promoting academic performance and professional excellence. Selected students attend mandatory seminars designed to provide academic support and a sense of camaraderie, with the aim of ensuring success in both programs. Initial outcomes indicate that the program inspired participants to reach their highest potential, academically and professionally. Nursing First scholars have excelled as newly employed registered nurses and as students in the university program.
Can Over-containment Prevent Recurrence in Children With Cerebral Palsy and Hip Dysplasia Undergoing Hip Reconstruction?
Authors: Zakrzewski Allyson M. , Bryant Austin J. , McCarthy James J.
Published: April 2022

Introduction:

Hip reconstruction is often necessary in children with cerebral palsy (CP) but is associated with high failure rates. Over-containment deeply seats the hip within the acetabulum at the time surgical reconstruction. The goal of this study is to evaluate the effect of over-containment on radiographic outcomes and failure rates in children with CP undergoing hip reconstruction.

Methods:

This study is a retrospective chart review of children with CP that underwent hip reconstruction between 2010 and 2019 with at least 2 years of radiographic follow-up. Migration percentage (MP), acetabular index (AI), and neck shaft angle (NSA) were recorded preoperatively, postoperatively and throughout follow-up. Failures were defined as a MP at latest follow-up ≥30% or need for revision hip reconstruction. Hips were divided into groups based on postoperative MP—group 1 (over-containment group) had a MP≤0% and group 2 had an MP>0%. Radiographic parameters and failure rates were compared across Gross Motor Functional Classification Score (GMFCS) level, age at the time of surgery, and degree of preoperative subluxation.

Results:

A cohort of 108 patients (197 hips) with an average age of 7.3±3.2 years met inclusion criteria with an average follow-up of 49.6 months (range: 24 to 118 mo). There were 147 hips in group 1 and 50 hips in group 2. At latest follow-up, group 1 demonstrated lower MP, AI, and NSA in comparison to group 2. The overall failure rate in our cohort was 8.1% (16 hips). Failure rates trended lowest in hips that were over-contained (6.1% v. 14.0%) although not statistically significant. Over-containment resulted in significantly lower failure rates in GMFCS IV/V hips, children under age 6 at the time of surgery and those with a higher degree of preoperative hip displacement (MP>50%).

Conclusions:

Over-containment at the time of hip reconstruction can positively affect radiographic outcomes and failure rates in children with CP. Over-containment should be considered in hips at high risk of failure, especially non ambulatory children with significant hip subluxation at an early age.

Level of Evidence:

Level III—retrospective comparative study.
Transanal Minimally Invasive Surgery for Rectal Anastomotic Stenosis After Colorectal Cancer Surgery
Authors: Zhou Wei , Xia Lian , Wang Zian , Cao Gaoyang , Chen Li , Chen Engeng , Zhang Wei , Song Zhangfa
Published: April 2022

BACKGROUND:

Anastomotic stenosis is a common complication of colorectal cancer surgery with anastomosis. Transanal minimally invasive surgery is a novel approach to the treatment of anastomotic stenosis.

OBJECTIVE:

This study aimed to evaluate the efficacy and safety of transanal minimally invasive surgery for anastomotic stenosis treatment.

DESIGN:

This was a retrospective study.

SETTINGS:

This study was conducted at a comprehensive cancer center.

PATIENTS:

This study included patients with rectal anastomotic stenosis who after undergoing colorectal surgery were admitted to the Sir Run Run Shaw Hospital between September 2017 and June 2019.

MAIN OUTCOME MEASURES:

The primary outcome was the operative success rate. The secondary outcomes were intraoperative variables, postoperative complications, stoma closure conditions, and stenosis recurrence risks.

RESULTS:

Nine patients, aged 52 to 80 years, with a history of colorectal cancer with end-to-end anastomosis underwent transanal minimally invasive surgery for anastomotic stenosis. The distance between the stenosis and the anal verge ranged from 5 to 12 cm. The mean stenosis diameter was 0.3 cm. Four patients had completely obstructed rectal lumens. Eight of 9 patients successfully underwent transanal minimally invasive surgery radial incision and cutting. The average operation time was 50 minutes. After the procedure, 1 patient had symptomatic procedure-associated perforations but recovered with conservative treatment. No perioperative mortality occurred. One patient underwent transverse colostomy 1 month after transanal minimally invasive surgery because of proximal colon ischemia induced by primary rectal surgery. Eight patients underwent protective loop ileostomy. After transanal minimally invasive surgery, stoma closure was performed in 88% of patients with no stenosis recurrence or obstruction at follow-up (21–42 mo).

LIMITATIONS:

This study was limited by its small sample size and single-center design.

CONCLUSIONS:

Transanal minimally invasive surgery provides an excellent operative field, good maneuverability, and versatile instrumentation and is a safe and effective treatment for rectal anastomotic stenosis, especially for severe fibrotic stenosis or complete obstruction. See Dynamic Article Video at http://links.lww.com/DCR/B965.
Acellular Dermal Matrices in Breast Reconstruction: CARE Trial 5-Year Outcomes Data for More Than 9500 Patients
Authors: Ellsworth Warren A. , Hammer Jason , Luo Lei , Schumacher Andrew
Published: April 2022

Background:

Few studies have assessed long-term complications in women undergoing implant-based breast reconstruction with use of an acellular dermal matrix (ADM). This study compared outcomes over 5 years in women undergoing breast reconstruction procedures with and without ADM.

Methods:

Complications data in patients enrolled in the prospective Continued Access Reconstruction/Revision Expansion trial were segregated by use of ADM versus no ADM in patients undergoing primary breast reconstruction or revision-reconstruction. Continued Access Reconstruction/Revision Expansion trial evaluated long-term safety and effectiveness of shaped, textured, silicone implants.

Results:

Of the 9502 women, 257 had primary (n = 160) or revision-reconstruction (n = 97) with ADMs; 9245 had primary (n = 6977) or revision-reconstruction (n = 2268) without ADMs. Capsular contracture rates in primary reconstruction were lower with ADM than without at year 5 (3.2% versus 7.4%); rates were similar at year 1 (≤2.4%). Capsular contracture rates in revision-reconstruction were lower with ADM than without at year 5 (1.4% versus 8.9%); rates were similar at year 1 (≤2.5%). Seroma rates were low and sustained for all cohorts throughout the 5 years (≤2.9%). Reoperation rates increased over time in all cohorts, with similar rates between groups (2.4%–47.3% from week 4 to year 5 across cohorts). Other trends over time included lower rates for asymmetry and implant malposition with ADM than without.

Conclusion:

These long-term data suggest that the use of ADM in breast reconstruction procedures may provide a benefit in reducing complications, such as capsular contracture, and may sustain low rates of seroma.
Imported Infectious Diseases, Tropical Diseases and Local Endemic Infectious Diseases in Japan
Authors: Toizumi Michiko , Horikoshi Yuho
Published: April 2022

We aimed to describe the historical perspectives and the current epidemiology of tropical, imported and local endemic infectious diseases in Japan in this review. Public health legislation for infectious diseases and immigration statistics were overviewed to provide the background of the infectious disease situation in Japan. Many tropical diseases were successfully controlled and eliminated in the latter half of the 20th century and the majority of those diseases are imported today. The trend of the main 15 imported infectious diseases before the advent of COVID-19 was summarized as well as local endemic infectious diseases in Japan. Transmission risks of traditional cuisines, lifestyles and nature exposures in Japan are introduced to guide clinicians for travel advice to prevent those local infectious diseases.
Sequelae at Hospital Discharge in 61 Children With Invasive Meningococcal Disease, Chile, 2009–2019
Authors: Arteta-Acosta Cindy , Villena Martínez Rodolfo , Santolaya de Pablo Maria Elena
Published: April 2022

Background:

Invasive meningococcal disease (IMD) is an unpredictable and severe infection caused by Neisseria meningitidis. Its case fatality rate could vary from 9.7% to 26% and up to 36% of survivors may experience long-term sequelae, representing a challenge for public health.

Aimed:

To describe the sequelae at hospital discharge caused by IMD in children between years 2009–2019.

Methods:

Cross-sectional study performed in 2 pediatric hospitals. Patients with microbiologically confirmed diagnosis of IMD from 2009 to 2019 were included. Bivariate and logistic regression analysis were performed.

Results:

The records of 61 patients were reviewed and included. Sixty-seven percent were male, median age 9 months (interquartile range 4–27), 72% were admitted to intensive care unit. Thirty-seven (60.5%) had at least 1 sequela (75% and 37% in patients with or without meningitis, respectively). The most frequents sequelae were neurological 72%, hearing loss 32%, and osteoarticular 24%. Significant differences were found comparing patients with and without sequelae: drowsiness 67.6% versus 41.7% (P = 0.04), irritability 67.6% versus 25% (P = 0.01), meningeal signs 62.2% versus 29.2% (P = 0.01). In logistic regression analysis, postdischarge follow-up had OR 21.25 (95% confidence intervals [CI]: 4.93–91.44), irritability had OR 8.53 (95% CI: 1.64–44.12), meningeal signs had OR 8.21 (95% CI: 0.71–94.05), invasive mechanical ventilation had OR 8.23 (95% CI: 0.78–85.95), meningitis plus meningococcemia OR 1.70 (95% CI: 0.18–15.67) to have sequelae, while children with meningococcemia and vomiting had a OR 0.04 (95% CI: 0.00–0.36) and OR 0.27 (95% CI: 0.03–2.14), respectively. N. meningitidis serogroup W (MenW) was isolated in 54.1% (33/61), and N. meningitidis serogroup B (MenB) in 31.1% (19/61) of cases. A significant difference was found in osteoarticular sequelae (P = 0.05) between MenB and MenW. There was a decrease in cases after the meningococcal conjugate vaccine against serogroups A, C, W and Y was implemented (2015–2019).

Conclusions:

IMD remains as a public health concern. A high rate of sequelae was found in pediatric patients in our series, even in the clinical manifestations other than meningitis. Neurological sequelae were the most prevalent. Multidisciplinary follow-up protocols to reduce long-term impact must be urgently established to assess all children with IMD
The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial
Authors: Lillemon Jennifer Nicole , Karstens Lisa , Nardos Rahel , Garg Bharti , Boniface Emily R. , Gregory W. Thomas
Published: April 2022

Importance

The postmenopausal urinary bladder microbiome is not well defined.

Objectives

The aims of this study were to characterize the effect of vaginal estrogen on the vaginal and urinary bladder microbiome in postmenopausal women and describe any clinical associations with the symptoms of genitourinary syndrome of menopause.

Study Design

This was a participant-masked, randomized controlled trial comparing the effect of a 12-week course of an estrogen-containing vaginal ring to a placebo vaginal ring. Standardized evaluations were performed at baseline and 12 weeks. Vaginal samples were obtained for pH, vaginal maturation index, and microbiome analysis. Concomitant catheterized urine samples were obtained for microbiome analysis. 16S ribosomal RNA gene sequencing was performed to characterize the resident microbial communities, with Lactobacillus relative abundance as the primary outcome variable. Genitourinary syndrome of menopause symptoms was measured using validated questionnaires (Pelvic Floor Distress Inventory–Short Form, Female Sexual Function Index, Vulvovaginal Symptoms Questionnaire).

Results

Of the 39 postmenopausal women randomized, baseline characteristics were similar between arms, with a mean age of 62 years and mean vaginal pH of 5.0. Using intention-to-treat analysis, there were no significant changes in vaginal or urinary Lactobacillus relative abundance. Two participants in each arm removed their ring prior to the end of the study. Eighty percent of participants experienced at least 1 bothersome genitourinary syndrome of menopause symptom. Vulvovaginal dryness and urinary frequency were most common at baseline, whereas painful intercourse and urinary urgency were most common at the final visit, none of which were statistically significant.

Conclusions

Our study did not show a significant change in the bacterial composition of the vaginal or urinary bladder microbiome after either vaginal ring in this relatively asymptomatic postmenopausal population.
Assessment of Suvorexant and Eszopiclone as Alternatives to Benzodiazepines for Treating Insomnia in Patients With Major Depressive Disorder
Authors: Shigetsura Yuki , Imai Satoshi , Endo Hiroki , Shimizu Yumi , Ueda Keita , Murai Toshiya , Itohara Kotaro , Nakagawa Shunsaku , Yonezawa Atsushi , Ikemi Yasuaki , Fukatsu Sachio , Kitada Noriaki , Terada Tomohiro , Nakagawa Takayuki , Matsubara Kazuo
Published: April 2022

Objectives

We investigated the utility of switching from benzodiazepines to suvorexant or eszopiclone to manage benzodiazepine-unresponsive insomnia in patients with major depressive disorder (MDD) in a randomized, open-label study.

Methods

Patients with MDD who have insomnia symptoms (a score of >7 on the Insomnia Severity Index Japanese version [ISI-J]), who had received benzodiazepine treatment for more than 2 weeks (n = 18) were randomized to 4 weeks of suvorexant (20 or 15 mg/d) or eszopiclone (3 or 2 mg/d) treatment. The primary endpoint was an improvement in insomnia severity from baseline assessed by the ISI-J score at 2 and 4 weeks after switching from benzodiazepines. The secondary endpoints included changes in the scores of the Pittsburgh Sleep Quality Index Japanese version, the Beck Depression Inventory II, Generalized Anxiety Disorder 7, the digit span test, and the digit symbol substitution test from baseline. Adverse events were recorded throughout the study.

Results

Patients taking suvorexant or eszopiclone had improved ISI-J scores (−4.3 for suvorexant and −4.1 for eszopiclone at week 4; P = 0.04 for eszopiclone). Both drugs tended to improve the Beck Depression Inventory II and Generalized Anxiety Disorder 7 scores 2 and 4 weeks after switching. The Pittsburgh Sleep Quality Index Japanese version, digit symbol substitution test, and digit span test scores and the incidence of adverse events did not change from baseline.

Conclusions

Switching to suvorexant or eszopiclone was well tolerated and improved the severity of benzodiazepine-unresponsive insomnia in MDD patients. Both drugs could be beneficial alternatives to benzodiazepines for treating insomnia in MDD patients.
Effectiveness and Safety of Early High-Efficacy Versus Escalation Therapy in Relapsing-Remitting Multiple Sclerosis in Argentina
Authors: Rojas Juan Ignacio , Patrucco Liliana , Alonso Ricardo , Garcea Orlando , Deri Norma , Carnero Contentti Edgar , Lopez Pablo A. , Pettinicchi Juan Pablo , Caride Alejandro , Cristiano Edgardo
Published: April 2022

Escalation (ES) and early high-efficacy (EHE) therapies have been the main treatment strategies adopted in multiple sclerosis (MS) in recent years. The aim of this study was to compare the effectiveness and safety of EHE versus ES strategies in MS patients from Argentina.

Methods

This is a retrospective multicenter cohort study in Argentina. Eligible patients were categorized into 2 groups as follows: EHE if received natalizumab, ocrelizumab, rituximab, alemtuzumab, mitoxantrone, or cladribine; and ES if received interferon β, glatiramer acetate, teriflunomide, dimethyl fumarate, or fingolimod as initial therapy. The primary outcome was confirmed disability progression (Expanded Disability Status Scale [EDSS] increase). Additional outcomes included the proportion of patients and time to: EDSS 6; new relapses; new T2–magnetic resonance imaging (MRI) lesions; no evidence of disease activity; and specific adverse events. Propensity score–based nearest-neighbor matching (without replacement) was applied to homogenize the sample, and Cox regression model stratified by matched pairs was used for the analysis.

Results

After propensity score matching, 193 and 112 patients were retained in the ES and EHE groups, respectively. The EHE significantly decreased the risk of EDSS progression (hazard ratio [HR], 0.62; 95% confidence interval [95% CI], 0.40–0.98; P = 0.04), relapses (HR, 0.66; 95% CI, 0.49–0.89; P = 0.006), and new MRI activity during follow-up (HR, 0.55; 95% CI, 0.40–0.75; P < 0.001). No significant differences were observed in specific adverse events between groups.

Conclusions

Our study shows that EHE therapies prevent disease progression, relapses, and new MRI lesions and demonstrated no increased risk of specific adverse events when compared with ES therapy. These data should be considered when selecting a specific treatment for MS patients.
Patient Personality and Illness Perceptions in Relation to Follow-Up Appointment Adherence in Neuro-Ophthalmology
Authors: Aziz Rem , Bindiganavale Megha P. , Chang Robert T. , Moss Heather E.
Published: April 2022

Background:

Improving patient attendance at medical follow-up visits may have a notable impact on disease and overall health outcomes. Understanding factors contributing to poor attendance is important for identifying at-risk patients and designing interventions to improve clinical outcomes. Our objective was to identify personality and illness perception factors associated with attendance at recommended follow-up visits in a neuro-ophthalmology practice.

Methods:

New or established patients (≥18 years) with scheduled neuro-ophthalmology (study) or glaucoma (comparison) appointments at a tertiary care academic medical center completed the Brief Illness Perception Questionnaire and Ten-Item Personality Inventory. Physician recommendations made during the visit were recorded (medications, referrals, follow-up, testing, and procedures). A chart review was performed 18 months after enrollment to assess attendance at follow-up appointment and adherence with other physician recommendations. Multiple variable logistic regression models studied associations between follow-up appointment attendance and demographic factors, appointment factors, and survey responses.

Results:

Among 152 respondents (97% response rate (152 of 157), aged 19–97 years, 58% female, 34% new, 80 neuro-ophthalmology, 72 glaucoma), neuro-ophthalmology subjects were younger, more likely to be White, non-Hispanic, female and new to the practice than subjects with glaucoma. They reported higher emotional impact, identity, and consequences related to their illness (P = 0.001–0.03). Neuro-ophthalmology physician recommendations included more referrals to other services (17.5% vs 1.4%, P = 0.001, chi-square) and more radiology studies (15% vs 0%, P = 0.001, chi-square), but fewer follow-up visits (75% vs 97%, P < 0.0005, chi-square). Among those with recommended follow-up visits, neuro-ophthalmology subjects had lower rates of on-time appointment attendance (55% vs 77%, P = 0.009, chi-square). In a multiple variable model, on-time follow-up attendance was associated with shorter recommended follow-up interval (≤90 days, P < 0.0005), established (vs new) patient status at enrollment visit (P = 0.04), and glaucoma (P = 0.08), but not subject demographics, illness perception, or personality factors.

Conclusions:

Patient demographics, illness perception, and personality traits were not associated with follow-up appointment attendance and therefore unlikely to be useful for identifying patients at risk of being lost to follow-up. New neuro-ophthalmology patients with a follow-up recommended ≥90 days in advance may benefit from targeted interventions to improve follow-up appointment adherence.
Peripapillary Microvascular and Structural Parameters in Atrophic Nonarteritic Anterior Ischemic Optic Neuropathy and Their Unaffected Fellow Eyes
Authors: Hondur Gozde , Budakoglu Ozlem
Published: April 2022

Background:

This cross-sectional study aimed to evaluate the peripapillary vessel density (VD), peripapillary retinal nerve fiber layer (RNFL) thickness values of eyes with atrophic nonarteritic anterior ischemic optic neuropathy (NAION), and unaffected fellow eyes.

Methods:

Peripapillary VDs and RNFL thicknesses in the peripapillary region and 4 sectors (superior, inferior, nasal, and temporal) were evaluated using optical coherence tomography angiography among 19 atrophic NAION eyes, 19 unaffected fellow eyes, and 22 age-matched and sex-matched healthy controls.

Results:

The NAION eyes had lower peripapillary VD and RNFL thickness values in all areas compared with both the fellow and the healthy control eyes (P < 0.001 for all). The fellow eyes also demonstrated lower peripapillary VD values (P = 0.02) despite similar RNFL thickness values (P = 0.99) in the peripapillary region compared with the age-matched and sex-matched healthy controls. The peripapillary RNFL thickness values significantly correlated with peripapillary VD values in both NAION and fellow eyes.

Conclusions:

Diminished RNFL thickness and peripapillary VD values were observed in atrophic NAION eyes. In addition, a tendency for a lower peripapillary VD despite similar RNFL thickness values in the fellow eyes may indicate the potential vascular risk factors for NAION.
Level and duration of IgG and neutralizing antibodies to SARS-CoV-2 in children with symptomatic or asymptomatic SARS-CoV-2 infection
Authors: Khaitan Alka , Datta Dibyadyuti , Bond Caitlin , Goings Michael , Co Katrina , Odhiambo Eliud O. , Zhang Lin , Beasley Stephanie , Poorbaugh Josh , John Chandy C.
Published: April 2022

Background

There are presently conflicting data about level and duration of antibodies to SARS-CoV-2 in children after symptomatic or asymptomatic infection.

Methods

We enrolled adults and children in a prospective 6-month study in the following categories: 1) symptomatic, SARS-CoV-2 PCR+ (SP+; children, n=8; adults, n=16), 2) symptomatic, PCR- or untested (children, n=27), 3) asymptomatic exposed (children, n=13) and 4) asymptomatic, no known exposure (children, n=19). Neutralizing and IgG antibodies to SARS-CoV-2 antigens and Spike protein variants were measured by multiplex serological assays.

Results

All SP+ children developed nAb, whereas 81% of SP+ adults developed nAb. Decline in the presence of nAb over 6 months was not significant in symptomatic children (100% to 87.5%, p=0.32) in contrast to adults (81.3 to 50.0%, p=0.03). Among all children with nAb (n=22), nAb titers and change in titers over 6 months were similar in symptomatic and asymptomatic children. Levels of IgG antibodies in children to the SARS-CoV-2 Spike, RBD-1 and -2, nucleocapsid and N-terminal domain antigens and to Spike protein variants were similar to those in adults. IgG levels to primary antigens decreased over time in both children and adults, but levels to three of six Spike variants decreased only in children.

Conclusions

Children with asymptomatic or symptomatic SARS-CoV-2 infection develop robust neutralizing antibodies that remain present longer than in adults but wane in titer over time, and broad IgG antibodies that also wane in level over time.

Key Points

Children have robust neutralizing and IgG antibody responses to SARS-CoV-2 infection after symptomatic or asymptomatic disease that are at least as strong as in adults. Neutralizing antibodies in children last longer than in adults but wane over time.
Evaluation of machine learning for predicting COVID-19 outcomes from a national electronic medical records database
Authors: Browning Sean , Lee Scott H. , Belay Ermias , DeCuir Jennifer , Cato Shana Godfred , Patel Pragna , Schwartz Noah , Wong Karen K.
Published: April 2022

Objective

When novel diseases such as COVID-19 emerge, predictors of clinical outcomes might be unknown. Using data from electronic medical records (EMR) allows evaluation of potential predictors without selecting specific features a priori for a model. We evaluated different machine learning models for predicting outcomes among COVID-19 inpatients using raw EMR data.

Materials and Methods

In Premier Healthcare Data Special Release: COVID-19 Edition (PHD-SR COVID-19, release date March, 24 2021), we included patients admitted with COVID-19 during February 2020 through April 2021 and built time-ordered medical histories. Setting the prediction horizon at 24 hours into the first COVID-19 inpatient visit, we aimed to predict intensive care unit (ICU) admission, hyperinflammatory syndrome (HS), and death. We evaluated the following models: L2-penalized logistic regression, random forest, gradient boosting classifier, deep averaging network, and recurrent neural network with a long short-term memory cell.

Results

There were 57,355 COVID-19 patients identified in PHD-SR COVID-19. ICU admission was the easiest outcome to predict (best AUC=79%), and HS was the hardest to predict (best AUC=70%). Models performed similarly within each outcome.

Discussion

Although the models learned to attend to meaningful clinical information, they performed similarly, suggesting performance limitations are inherent to the data.

Conclusion

Predictive models using raw EMR data are promising because they can use many observations and encompass a large feature space; however, traditional and deep learning models may perform similarly when few features are available at the individual patient level.
In macrophages fatty acid oxidation spares glutamate for use in diverse metabolic pathways required for alternative activation
Authors: van Teijlingen Bakker Nikki , Flachsman Lea , Carrizo Gustavo E. , Sanin David E. , Lawless Simon , Castoldi Angela , Monteiro Lauar , Kabat Agnieszka M. , Matsushita Mai , Haessler Fabian , Patterson Annette , Geltink Ramon Klein , O’Sullivan David , Pearce Erika L. , Pearce Edward J.
Published: April 2022

Fatty acid oxidation (FAO) is upregulated in IL-4-stimulated (alternatively activated) macrophages (M(IL-4)). We examined the effect of loss of function of the enzyme Cpt1a, which facilitates the entry of long chain fatty acids (FA) into mitochondria for FAO, on alternative activation. Expression of M(IL-4) markers ARG1, CD301 and RELMα, was impaired in tamoxifen-treated ERT2Cre x Cpt1afl/fl macrophages and in macrophages expressing shRNA targeting Cpt1a (Cpt1a-shRNA). In contrast, VaviCre x Cpt1afl/fl and LysmCre x Cpt1afl/fl M(IL-4) responded normally to IL-4. Reduced alternative activation due to Cpt1a loss of function was linked to decreased cellular pools of α-ketoglutarate, glutamate, and glutathione, diminished commitment of glucose carbon to serine/glycine synthesis, and decreased expression of genes in the Nrf2-oxidative stress response pathway. Consistent with this, reactive oxygen species were increased. Restoration of glutathione pools with N-acetyl cysteine normalized oxidative stress and allowed alternative activation in the face of Cpt1a-deficiency, pointing to a role for FAO in the control of ROS and as being important for alternative activation. In VaviCre x Cpt1afl/fl M(IL-4), glutamine uptake was increased, compensating for the loss of FAO to meet necessary metabolic demands, to allow alternative activation. The data indicate that macrophages are able to regulate glutamine metabolism to compensate for chronic disruption of FAO to meet metabolic needs.
Profiling the size-dependent heterogeneity of membrane proteins in a mixed population of small extracellular vesicle for potential cancer diagnosis
Authors: Zhai Chunhui , Xie Feng , Zeng Qiang , Zheng Weiqiang , Wang Jingan , Hu Haiyan , Yang Yuting , Ding Xianting , Yu Hui
Published: April 2022

The heterogeneity in small extracellular vesicles (small EVs) introduces an extra level of complexity in small EV-based liquid biopsy for cancer diagnosis. Heterogeneous membrane protein expression is correlated with sizes of small EVs, but accessing this correlative information is limited by the precise isolation of size-dependent subpopulations. Herein, we present a single EV enumeration (SEVEN) approach to profile protein heterogeneity in size-dependent subpopulations, and demonstrate its potential in improving the accuracy of cancer diagnosis. The interferometric plasmonic microscopy (iPM) capable of imaging single biological nanoparticles with the diameter down to 30 nm is employed to detect small EVs at the single-particle level. Small EVs population with mixed sizes are directly imaged, individually sized and digitally counted during their binding onto different aptamer-coated iPM sensor surfaces. The protein expression levels and binding kinetics of three size-dependent subpopulations are analyzed, forming a multidimensional data matrix for cancer diagnosis. Using small EVs derived from different cancer cell lines, highly heterogeneous protein profiles are recorded in the three subpopulations. We further demonstrate that the cancer classification accuracy could be greatly improved by including the subpopulation level heterogeneous protein profiles as compared with conventional ensemble measurement.
A Third Somatomotor Representation in the Human Cerebellum
Authors: Saadon-Grosman Noam , Angeli Peter A. , DiNicola Lauren M. , Buckner Randy L.
Published: April 2022

Seminal neurophysiological studies in the 1940s discovered two somatomotor maps in the cerebellum – an inverted anterior lobe map and an upright posterior lobe map. Both maps have been confirmed in the human using non-invasive neuroimaging with additional hints of a third map near to the cerebellar vermis. Here we sought direct evidence for the third somatomotor map by using intensive, repeated functional MRI (fMRI) scanning of individuals performing movements across multiple body parts (tongue, hands, glutes and feet). An initial discovery sample (N=4, 4 sessions per individual including 576 separate blocks of body movements) yielded evidence for the two established cerebellar somatomotor maps, as well as evidence for a third discontinuous foot representation near to the vermis. When the left versus right foot movements were directly contrasted, the third representation could be clearly distinguished from the second representation in multiple individuals. Functional connectivity from seed regions in the third somatomotor representation confirmed anatomically-specific connectivity with the cortex, paralleling the patterns observed for the two well-established maps. All results were prospectively replicated in an independent dataset with new individuals (N=4). These collective findings provide direct support for a third somatomotor map in the vermis of the cerebellum. We discuss the relations of this candidate third map to the broader topography of the cerebellum as well as its implications for understanding the specific organization of the human cerebellar vermis where distinct zones appear functionally specialized for somatomotor and visual domains.
Innovations in freight transport: a systematic literature evaluation and COVID implications
Authors: Kiani Mavi Reza , Kiani Mavi Neda , Olaru Doina , Biermann Sharon , Chi Sae
Published: April 2022

Purpose

This paper systematically evaluates the existing literature of innovations in freight transport, including all modes, to uncover the key research themes and methodologies employed by researchers to study innovations and their implications in this industry. It analyses the role of transport and the impact of innovations during crises, such as COVID-19.

Design/methodology/approach

Qualitative and quantitative analysis of the innovations in freight transport unravels the pre-requisites of such endeavours in achieving a resilient and sustainable transport network that effectively and efficiently operates during a crisis. The authors performed keyword co-occurrence network (KCON) analysis and research focus parallelship network (RFPN) analysis using BibExcel and Gephi to determine the major resulting research streams in freight transport.

Findings

The RFPN identified five emerging themes: transport operations, technological innovation, transport economics, transport policy and resilience and disaster management. Optimisation and simulation techniques, and more recently, artificial intelligence and machine learning (ML) approaches, have been used to model and solve freight transport problems. Automation innovations have also penetrated freight and supply chains. Information and communication technology (ICT)-based innovations have also been found to be effective in building resilient supply chains.

Research limitations/implications

Given the growth of e-commerce during COVID-19 and the resulting logistics demand, along with the need for transporting food and medical emergency products, the role of automation, optimisation, monitoring systems and risk management in the transport industry has become more salient. Transport companies need to improve their operational efficiency using innovative technologies and data science for informed decision-making.

Originality/value

This paper advises researchers and practitioners involved in freight transport and innovation about main directions and gaps in the field through an integrated approach for evaluating research undertaken in the area. This paper also highlights the role of crisis, e.g. COVID-19, and its impacts on freight transport. Major contributions of this paper are as follows: (1) a qualitative and quantitative, systematic and effective assessment of the literature on freight transport through a network analysis of keywords supplemented by a review of the text of 148 papers; (2) unravelling major research areas; (3) identifying innovations in freight transport and their classification as technological and non-technological and (4) investigating the impact of crises and disruptions in freight transport.