bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood vaccination and allergy: A systematic review and meta‐analysis
Authors: Navaratna Samidi , Estcourt Marie J. , Burgess John , Waidyatillake Nilakshi , Enoh Elizabeth , Lowe Adrian J. , Peters Rachel , Koplin Jennifer , Dhamage Shyamali C. , Lodge Caroline J.
Published: February 2021

Background and Objective

As the rise in prevalence of allergic diseases worldwide corresponds in time with increasing infant vaccination, it has been hypothesized that childhood vaccination may increase the risk of allergic disease. We aimed to synthesize the literature on the association between childhood vaccination and allergy.

Design

We searched the electronic databases PubMed and EMBASE (January 1946‐January 2018) using vaccination and allergy terms.

Methods

Two authors selected papers according to the inclusion criteria. Pooled effects across studies were estimated using random‐effects meta‐analysis. Due to inadequate number of homogeneous publications on newer and underused vaccines, meta‐analysis was limited to allergic outcomes following administration of (Bacillus Calmette‐Guérin) BCG, measles or pertussis vaccination. The review was prospectively registered in the PROSPERO systematic review registry (NO: CRD42017071009).

Results

A total of 35 publications based on cohort studies and 7 publications based on randomized controlled trials (RCTs) met the inclusion criteria. RCTs: From 2 studies, early vaccination with BCG vaccine was associated with a reduced risk of eczema (RR = 0.83; 95% CI = 0.73‐0.93; I2 = 0%) but not food allergy or asthma. No association was found between pertussis vaccine and any allergic outcome based on a single RCT.

Cohort studies

Childhood measles vaccination was associated with a reduced risk of eczema (RR = 0.65; 95% CI = 0.47‐0.90, I2 = 0.0%), asthma (RR = 0.78; 95% CI = 0.62‐0.98, I2 = 93.9%) and, with a similar, statistically non‐significant reduction in sensitization (RR = 0.78; 95% CI = 0.61‐1.01, I2 = 19.4%).

Conclusions

We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease. Our results from pooled analysis of both RCTs and cohort studies suggest that vaccination with BCG and measles vaccines were associated with a reduced risk of eczema.
Allergen immunotherapy: The growing role of observational and randomized trial “Real‐World Evidence”
Authors: Paoletti Giovanni , Di Bona Danilo , Chu Derek K. , Firinu Davide , Heffler Enrico , Agache Ioana , Jutel Marek , Klimek Ludger , Pfaar Oliver , Mösges Ralph , DunnGalvin Audrey , Genuneit Jon , Hoffmann Hans Jürgen , Canonica Giorgio Walter
Published: February 2021

Background

Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real‐world evidence (RWE) in AIT, and consequently, a lack of information on how AIT effectively works in real life.

Methods

To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic “real‐world” database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence.

Key Results

There is a need to establish more AIT registries that collect data in a cohesive way, using standardized protocols.

Conclusions

This will provide an essential source of real‐world data that can be easily shared, promoting evidence‐based research and quality improvement in study design and clinical decision‐making.
Duration of post‐operative antibiotic treatment in acute complicated appendicitis: systematic review and meta‐analysis
Authors: Ramson Dhruvesh M. , Gao Hugh , Penny‐Dimri Jahan C. , Liu Zhengyang , Khong Jacqueline Nguyen , Caruana Carla B. , Campbell Ryan , Jackson Sarah , Perry Luke A.
Published: February 2021

Background

Appendicitis is the most frequent aetiology of acute abdominal pain requiring surgical treatment, with an estimated lifetime risk between 7% and 8%. Antibiotics play a substantial role in treatment, and there is considerable debate regarding the duration of antibiotics in treating appendicitis.

Methods

We searched multiple databases from inception until June 2019 for peer‐reviewed studies that compared different durations of antibiotic treatment after appendicectomy for acute complicated appendicitis in adults. We dichotomized reported data into short‐ and extended‐term antibiotic use and controlled for different definitional thresholds in the meta‐analysis. We generated risk ratios using restricted maximum likelihood methods and mixed effects modelling for each outcome of interest.

Results

Four observational studies involving 847 participants were included in the meta‐analysis. For the primary outcomes of intra‐abdominal infection, we did not find a statistically significant difference between extended‐ and short‐term antibiotic strategies for intra‐abdominal infection (Risk ratio 0.92, 95% confidence interval (CI) 0.49–1.74). Three randomized controlled trials involving 291 participants were included in a separate meta‐analysis. We found that extended antibiotic usage was not associated with a statistically significant reduced risk for intra‐abdominal infection (RR 0.52, 95% CI 0.21–1.29) or surgical site skin infection (RR 1.44, 95% CI 0.43–4.81).

Conclusion

This systematic review and meta‐analysis found that extended post‐operative antibiotic treatment may not be associated with a reduced risk of intra‐abdominal infection; however, meta‐analysis was significantly limited by heterogeneity between studies and underpowered trials. Further large randomized controlled trials are needed to confirm these findings.
Postoperative serum procalcitonin versus C‐reactive protein as a marker of postoperative infectious complications in pancreatic surgery: a meta‐analysis
Authors: Vasavada Bhavin , Patel Hardik
Published: February 2021

Background

Aim of this meta‐analysis was to compare diagnostic accuracy C‐reactive protein and procalcitonin between postoperative days 3 and 5 to predict infectious complications post pancreatic surgery.

Methods

A systemic literature search was performed using MEDLINE, EMBASE and SCOPUS to identify studies evaluating the diagnostic accuracy of procalcitonin and C‐reactive protein to predict infectious complications between postoperative days 3 and 5 following pancreatic surgery. A meta‐analysis was performed using random‐effect model and pooled predictive parameters.

Results

Fifteen studies consisting of 2212 patients were included in the final meta‐analysis. Pooled sensitivity, specificity, area under curve and diagnostic odds ratio (DOR) for day 3 C‐reactive protein were 62%, 67%, 0.772 and 6.54, respectively. Pooled sensitivity, specificity, area under curve and DOR for day 3 procalcitonin were 74%, 79%, 0.8453 and 11.03, respectively. Sensitivity, specificity, area under the curve and DOR for day 4 C‐reactive protein were 60%, 68%, 0.8022 and 11.90, respectively. Sensitivity, specificity and DOR of postoperative day 5 procalcitonin level for predicting infectious complications were 83%, 70% and 12.9, respectively. Pooled sensitivity, specificity, Area Under Receiver Operating Curve and DOR were 50%, 70%, 0.777 and 10.19, respectively.

Conclusion

Postoperative procalcitonin is a better marker to predict postoperative infectious complications after pancreatic surgeries.
Maternal and newborn health risks of climate change: A call for awareness and global action
Authors: Roos Nathalie , Kovats Sari , Hajat Shakoor , Filippi Veronique , Chersich Matthew , Luchters Stanley , Scorgie Fiona , Nakstad Britt , Stephansson Olof ,   CHAMNHA Consortium
Published: February 2021

Climate change represents one of the largest global health threats of the 21st century with immediate and long‐term consequences for the most vulnerable populations, especially in the poorest countries with the least capacity to adapt to climate change. Pregnant women and newborns are increasingly being recognized as vulnerable populations in the context of climate change. The effects can be direct or indirect through heat stress, extreme weather events and air pollution, potentially impacting both the immediate and long‐term health of pregnant women and newborns through a broad range of mechanisms. In 2008, the World Health Organization passed a resolution during the 61st World Health Assembly, recognizing the need for research to identify strategies and health‐system strengthening to mitigate the effects of climate change on health. Climate adaptation plans need to consider vulnerable populations such as pregnant women and neonates and a broad multisectoral approach to improve overall resilience of societies.
Dry eye disease is associated with retinal microvascular dysfunction and possible risk for cardiovascular disease
Authors: Shokr Hala , Wolffsohn James S. , Trave Huarte Sonia , Scarpello Emily , Gherghel Doina
Published: February 2021

Purpose

To explore the presence of microvascular endothelial dysfunction as a measure for early cardiovascular disease in individuals diagnosed with dry eye disease (DED) as compared to age‐matched normal controls.

Methods

Systemic blood pressure, Body Mass Index, intraocular pressure, blood levels of glucose (GLUC), triglycerides, cholesterol (CHOL), high‐density lipoprotein cholesterol (HDL‐C), and low‐density lipoprotein cholesterol (LDL‐C)] as well as retinal and peripheral microvascular function were assessed in twenty‐five 35–50 year olds with diagnosed with DEDa (using the TFOS DEWS II criteria) and 25 age and sex‐matched controls.

Results

After controlling all the influential covariates, individuals diagnosed with DED exhibited significant lower retinal artery baseline (p = 0.027), artery maximum diameter (p = 0.027), minimum constriction (p = 0.039) and dilation amplitude (p = 0.029) than controls. In addition, the time to reach the vein maximum diameter was significantly longer in the DED patients than in normal controls (p = 0.0052). Only in individuals diagnosed with DED, artery maximum constriction correlated statistically significantly and positively with HDL‐C blood levels (p = 0.006). Similarly, artery slopeAD correlated positively with T‐CHOL and LDL‐C (p = 0.006 & 0.011 respectively). Additionally, artery baseline diameter and maximum constriction were significantly and negatively correlated to T‐CHOL/HDL‐C ratio (p = 0.032 and p = 0.013 respectively) in DED individuals only.

Conclusions

Individuals with positive diagnosis of DED exhibit abnormal retinal microvascular function and possible higher risk for CVD.
Comparison of efficacy and early surgery‐related complications between one‐quadrant and two‐quadrant microhook ab interno trabeculotomy: a propensity score matched study
Authors: Mori Sotaro , Murai Yusuke , Ueda Kaori , Sakamoto Mari , Kurimoto Takuji , Yamada‐Nakanishi Yuko , Nakamura Makoto
Published: February 2021

Purpose

We compared the 1‐year outcomes and early surgery‐related complications between 1‐quadrant and 2‐quadrant microhook ab interno trabeculotomy (TLO).

Methods

Medical chart extraction was performed on 47 consecutive patients with 1‐quadrant incision and 37 consecutive patients with 2‐quadrant incision of trabecular meshwork. Logistic regression analysis was conducted to calculate the propensity score to create a 1:1 match for a comparative analysis of 1‐year postoperative success. Success was defined as postoperative intraocular pressure (IOP) between 5–21 mmHg, >20% IOP reduction from baseline, and no additional glaucoma surgery. Outcome‐related covariates were age, glaucoma type, mean deviation of visual field tests, preoperative IOP, the number of preoperative glaucoma eye drops and the presence of combined cataract surgery. Thirty eyes from each group were compared.

Results

The median preoperative IOP was not different between the 1‐quadrant and 2‐quadrant groups (28.5 mmHg, quartile range 23–33.5 versus 27 mmHg, 23.3–30.0, p = 0.47). There was no difference in median postoperative IOP at 1 year (15 mmHg versus 16 mmHg, p = 0.80). The success rate was 73% in the 1‐quadrant group versus 70% in the 2‐quadrant group (p = 1.00). The 2‐quadrant group had a significantly higher proportion of patients with transiently elevated IOP (47%) than the 1‐quadrant (17%; Fisher's exact test, p = 0.02). There was no difference of hyphema formation (Fisher's exact test, p = 0.18).

Conclusion

The 1‐year success rate was not significantly different between 1‐ and 2‐quadrant incisions of microhook TLO. However, the 2‐quadrant TLO showed significantly higher proportion of post‐surgical transient IOP elevation.
Delayed diagnoses of Acanthamoeba keratitis at a tertiary care medical centre
Authors: Shah Yesha S. , Stroh Inna G. , Zafar Sidra , Zhang Nancy , Sriparna Manjari , Shekhawat Nakul , Ghos Zara , Srikumaran Divya , Woreta Fasika A.
Published: February 2021

Purpose

To determine the prevalence and reasons for delays in diagnosis in patients with Acanthamoeba keratitis (AK) presenting to Wilmer Eye Institute, Baltimore, Maryland.

Methods

This retrospective study analysed all patients with culture‐positive AK seen between 2012 and 2019 at a tertiary referral centre. Patient demographic information, clinical history, risk factors, symptom duration, referral patterns, slit lamp examination findings, visual acuity and need for surgery were collected.

Results

The study included 45 eyes of 43 patients. On average, patients were symptomatic for 52.6 days before culture collection. Thirty‐one percent of patients were diagnosed within 28 days of symptom onset while 69% were diagnosed after 28 days. Before presentation to a tertiary care centre, 69% of patients were evaluated by an ophthalmologist outside of this institution and 27% were evaluated by a provider other than an ophthalmologist. AK was most commonly misdiagnosed as herpetic keratitis, occurring in 38% of patients. The strongest risk factor for AK was contact lens use. Only 11% of patients presented with the classic ring infiltrate and 82% had pain. Patients with an early versus late diagnosis had a mean Snellen visual acuity (VA) of 20/224 versus 20/296 at presentation (p = 0.33) and a mean Snellen VA of 20/91 versus 20/240 at final visit (p = 0.07). 11% of patients required a therapeutic penetrating keratoplasty.

Conclusion

Delayed diagnosis of AK in our cohort occurred due to a misdiagnosis as herpetic keratitis, non‐specific clinical signs including the lack of pain in a number of patients, and a delay in referral to a tertiary care centre. Any contact lens wearer with an atypical keratitis should be referred promptly for Acanthamoeba cultures.
Genotype–phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials
Authors: Galbis‐Martínez Lilián , Blanco‐Kelly Fiona , García‐García Gema , Ávila‐Fernández Almudena , Jaijo Teresa , Fuster‐García Carla , Perea‐Romero Irene , Zurita‐Muñoz Olga , Jimenez‐Rolando Belén , Carreño Ester , García‐Sandoval Blanca , Millán José M. , Ayuso Carmen
Published: February 2021

Purpose

We aimed to establish correlations between the clinical features of a cohort of Usher syndrome (USH) patients with pathogenic variants in MYO7A, type of pathogenic variant, and location on the protein domain.

Methods

Sixty‐two USH patients from 46 families with biallelic variants in MYO7A were examined for visual and audiological features. Participants were evaluated based on self‐reported ophthalmological history and ophthalmological investigations (computerized visual field testing, best‐corrected visual acuity, and ophthalmoscopic and electrophysiological examination). Optical coherence tomography and fundus autofluorescence imaging were performed when possible. Auditory and vestibular functions were evaluated. Patients were classified according to the type of variant and the protein domain where the variants were located.

Results

Most patients displayed a typical USH1 phenotype, that is, prelingual severe‐profound sensorineural hearing loss, prepubertal retinitis pigmentosa (RP) and vestibular dysfunction. No statistically significant differences were observed for the variables analysed except for the onset of hearing loss due to the existence of two USH2 cases, defined as postlingual sensorineural hearing loss, postpubertal onset of RP, and absence of vestibular dysfunction, and one atypical case of USH.

Conclusion

We were unable to find a correlation between genotype and phenotype for MYO7A. However, our findings could prove useful for the assessment of efficacy in clinical trials, since the type of MYO7A variant does not seem to change the onset, severity or course of visual disease.
Primary and secondary superior rectus recessions to correct vertical deviations in Graves’ orbitopathy patients
Authors: Eckstein Anja , Oeverhaus Michael , Dekowski Dirk , Stöhr Mareile , Merckel‐Timmer Elly , Saeed Peerooz , Jellema Hinke‐Marijke
Published: February 2021

Purpose

Patients with vertical strabismus and consecutive diplopia due to Graves’ orbitopathy (GO) might need recession of the rectus superior muscle. The aim of this retrospective analysis is to provide dose–effect values and motility analysis for these patients.

Methods

Dose–effect relations (deviation reduction in primary position per amount of recession in mm), monocular excursions and size of the field of binocular single vision (BSV) were evaluated in three different groups of patients. Group 1 (n = 33) patients with primary fibrosis of superior rectus muscle undergoing recession of the ipsilateral rectus superior, Group 2 (n = 14) superior rectus muscle recession after recession of inferior rectus on the contralateral eye and Group 3 (n = 15) simultaneous ipsilateral superior rectus recession and contralateral inferior rectus muscle recession. Surgery was performed using the dose–effect for inferior rectus recession of 4 prism dioptre (PD,Δ) reduction/per mm recession and the intraoperative traction test.

Results

Restoration of BSV in the central 20° of gaze could be reached in 88%, 79% and 67% of patients in the three groups, respectively. Restoration of BSV in downgaze (up to 30°) was a little less successful, 79%, 57% and 53%, respectively. The median dose–effect was 3.2Δ reduction/mm recession in Group 1 (Spearman correlation r = 0.75, p < 0.0001) and 3.3Δ/mm in Group 2 (n.s.) and 4Δ/mm in Group 3 (r = 0.67, p = 0.016). The basis for the improvement was the symmetrization of ductions.

Conclusion

If superior rectus recession is necessary in GO, higher dosing around 3Δ reduction/per mm recession should be applied. In case of large deviations, combined vertical surgery (inferior rectus and superior rectus contralateral) is required and reasonable (low cyclotorsion). Single‐step or two‐step procedures lead to similar results.
Diagnosis of advanced gastric cancer using image enhancement and autofluorescence imaging systems
Authors: Matsui Ryota , Inaki Noriyuki , Tsuji Toshikatsu
Published: February 2021

Introduction

The indication of laparoscopic gastrectomy for advanced cases such as serosal invasion or peritoneal dissemination is still controversial. We report the clinical experiences of laparoscopic diagnosis with image enhancement and autofluorescence (AF) systems for laparoscopic gastric cancer surgery.

Methods

The image enhancement system was introduced to 164 patients who underwent laparoscopic gastric cancer surgery as the AF group. The control group was defined as 165 cases who underwent bright light observation without the image enhancement system. The operative findings were recorded during surgery. All image findings were retrospectively compared with the pathological findings. Furthermore, the relationship between the image and pathological findings for peritoneal dissemination and subserosal invasion was evaluated.

Results

This study included 329 patients, divided into the control group of 165 patients (50.2%) and the AF group of 164 patients (49.8%). There was no statistically significant difference in patient background between the two groups. In seven cases of peritoneal dissemination, AF was positive, and macroscopic abnormal vascularization was detected. The sensitivity, specificity, and positive and negative predictive values were 100%, 99.4%, 87.5%, and 100%, respectively. In 29 cases of serosal invasion, AF was positive, and macroscopic abnormal vascularization was detected. In the detection accuracy of subserosal invasion, the sensitivity, specificity, and positive and negative predictive values were 75.7%, 97.6%, 90.3%, and 93.2%, respectively.

Conclusion

The image enhancement with the AF system is useful for the laparoscopic intraoperative diagnosis of serosal invasion and peritoneal dissemination for advanced gastric cancer.
Explaining identity formation in Asia
Authors: Liu Amy H. , Selway Joel Sawat
Published: February 2021

What explains why some identities in a country become politically salient while others do not? This Special Issue crafts a research design to address two core assumptions in the literature on identity formation in select Asian countries. The first is that the area where ethnic groups reside is exogenously demarcated. Yet, the boundaries to any region are inherently political—for example, they can be endogenous to the same processes that drive identity formation. To address this, we take a novel approach by delineating regions exogenously by their cardinal directions in the country (e.g., north), and then, comparing among those regions to see which identities become salient and why. The second assumption is that there is always an alternative cleavage along which ethnic groups can coordinate. Yet, which cleavages are available and how ethnicity maps onto other cleavages (e.g., cross‐cutting) affects political identity. The articles in this Special Issue address this assumption by articulating and mapping a more complete set of cleavages. In doing so, the authors present a novel array of theories explaining the various stages along which identities fall, from absent to stunted, or from slow onset to fully solidified.
The telemedical imperative
Authors: Parsons Jordan A.
Published: February 2021

Technology presents a means of improving health outcomes for vast numbers of individuals. It has historically been deployed to streamline healthcare delivery and reach those who would previously have faced obstacles to accessing services. It has also enabled improved health education and management. Telemedicine can be employed in everything from primary care consultations to the monitoring of chronic diseases. Despite recommendation by the World Health Organization, countries have been slow to embrace such technology in the health sector. Nonetheless, it is expected to become more prevalent with increased digitization. Further, amidst the COVID‐19 pandemic, there was a rush to implement forms of telemedicine where possible to prevent patients breaking social distancing rules. In this paper, I present and defend what I term the ‘telemedical imperative’. The telemedical imperative represents a duty for healthcare systems to implement remote access to services where possible, thereby furthering the mission of equity in access to healthcare. It is intended as an addition to in‐person services rather than a replacement. After highlighting the benefits of telemedicine, I provide four criteria that must be met for the telemedical imperative to arise. The first three—safety, effectiveness, and acceptability—are consistent and essential. The fourth adapts to the service in question and requires that there be no other obstacles specific to that service that cannot reasonably be overcome. Finally, I address several potential objections to the telemedical imperative based on more general concerns around the implementation of telemedicine.
Perinatal depression in Pakistan: A systematic review and meta‐analysis
Authors: Atif Maria , Halaki Mark , Raynes‐Greenow Camille , Chow Chin‐Moi
Published: February 2021

Objective

To estimate the prevalence and associated risk factors of perinatal depression in Pakistan.

Methods

We conducted a systematic search of Medline, PsycINFO, CINAHL, EMBASE, and Global health, up through May 31, 2019. Studies reporting on the prevalence of perinatal depression in Pakistan with or without associated risks factors were included.

Results

Forty‐three studies reporting data from 17 544 women met the eligibility criteria and were included. Overall, the pooled prevalence of antenatal depression was 37% (95% CI: 30‐44), while that of postnatal depression was 30% (95% CI: 25‐36). The prevalence of perinatal depression in women residing in urban areas and those living in rural settings was not significantly different. The most frequently reported risk factors for antenatal depression were intimate partner violence and poor relationship with spouse, and that reported for postnatal depression was low‐income level. An unintended pregnancy was significantly associated with perinatal depression in Pakistan.

Conclusions

We identified variability in prevalence rate of perinatal depression in Pakistan. It is difficult to gauge the true magnitude of this problem potentially due to differing risk factors between the antenatal and postnatal periods and the lack of uniformity of data collection protocols and procedures. The high prevalence rates of 30%‐37% compared to global estimates suggest policy makers and stakeholders should direct additional resources toward improving perinatal mental health in Pakistan.
Perinatal outcomes of planned home birth after cesarean and planned hospital vaginal birth after cesarean at term gestation in British Columbia, Canada: A retrospective population‐based cohort study
Authors: Bayrampour Hamideh , Lisonkova Sarka , Tamana Sukhpreet , Wines Jane , Vedam Saraswathi , Janssen Patricia
Published: February 2021

Background

The aim of this retrospective population‐based cohort study was to determine whether the mode of delivery and maternal and neonatal outcomes differ between planned home VBAC (HBAC) and planned hospital VBAC.

Methods

All midwifery clients with at least one prior cesarean birth delivered between April 2000 and March 2017 (N = 4741; n = 4180 planned hospital VBAC, n = 561 planned HBAC) were included. Multivariate binomial logistic regression analyses were conducted to calculate the odds ratios adjusted for the potential covariates. The primary outcome was the mode of delivery, and the secondary outcomes were uterine rupture/dehiscence, postpartum hemorrhage, nonintact perineum, episiotomy, obstetric trauma, Apgar score <7 at 5 minutes, neonatal resuscitation requiring positive pressure ventilation, neonatal intensive care unit admission, and a composite outcome of severe neonatal mortality and morbidity and maternal mortality and morbidity.

Results

Planned HBAC was associated with a significant 39% decrease in the odds of having a cesarean birth (aOR 0.61, 95% CI 0.47‐0.79) adjusting for the prepregnancy and pregnancy characteristics. Severe adverse outcomes were relatively rare in both settings; thus, our study did not have sufficient power to detect the true differences associated with the place of birth.

Conclusions

Home births for those eligible for VBACs and attended by registered midwives within an integrated health system were associated with higher vaginal birth rates compared with planned hospital VBACs. Severe adverse outcomes were relatively rare in both settings.
Building an emotion regulation recommender algorithm for socially anxious individuals using contextual bandits
Authors: Beltzer Miranda L. , Ameko Mawulolo K. , Daniel Katharine E. , Daros Alexander R. , Boukhechba Mehdi , Barnes Laura E. , Teachman Bethany A.
Published: February 2021

Objectives

Poor emotion regulation (ER) has been implicated in many mental illnesses, including social anxiety disorder. To work towards a scalable, low‐cost intervention for improving ER, we developed a novel contextual recommender algorithm for ER strategies.

Design

N = 114 socially anxious participants were prompted via a mobile app up to six times daily for five weeks to report their emotional state, use of 19 different ER strategies (or no strategy), physical location, and social context. Information from passive sensors was also collected.

Methods

Given the large number of ER strategies, we used two different approaches for variable reduction: (1) grouping ER strategies into categories based on a prior meta‐analysis, and (2) considering only the ten most frequently used strategies. For each approach, an algorithm that recommends strategies based on one’s current context was compared with an algorithm that recommends ER strategies randomly, an algorithm that always recommends cognitive reappraisal, and the person’s observed ER strategy use. Contextual bandits were used to predict the effectiveness of the strategies recommended by each policy.

Results

When strategies were grouped into categories, the contextual algorithm was not the best performing policy. However, when the top ten strategies were considered individually, the contextual algorithm outperformed all other policies.

Conclusions

Grouping strategies into categories may obscure differences in their contextual effectiveness. Further, using strategies tailored to context is more effective than using cognitive reappraisal indiscriminately across all contexts. Future directions include deploying the contextual recommender algorithm as part of a just‐in‐time intervention to assess real‐world efficacy.

Practitioner points

Emotion regulation strategies vary in their effectiveness across different contexts.

An algorithm that recommends emotion regulation strategies based on a person’s current context may one day be used as an adjunct to treatment to help dysregulated individuals optimize their in‐the‐moment emotion regulation.

Recommending flexible use of emotion regulation strategies across different contexts may be more effective than recommending cognitive reappraisal indiscriminately across all contexts.
Absence of hydroxyurea‐induced mutational effects supports higher utilisation for the treatment of sickle cell anaemia
Authors: Ware Russell E. , Dertinger Stephen D.
Published: February 2021

Hydroxyurea (hydroxycarbamide) is approved for treating both children and adults with sickle cell anaemia (SCA). Fetal haemoglobin (HbF) induction is the primary treatment response, along with improved anaemia, reduced haemolysis, myelosuppression and decreased endothelial inflammation. Hydroxyurea has proven clinical efficacy for SCA — treatment significantly reduces disease manifestations and prolongs survival. Despite these recognised benefits, long‐standing concerns regarding the risks of mutagenic and potentially carcinogenic drug exposure have hampered efforts for broad hydroxyurea use in SCA, although these are based largely on outdated experimental models and treatment experiences with myeloproliferative neoplasms. Consequently, many patients with SCA are not receiving this highly effective disease‐modifying therapy. In this review, we describe the concept of genotoxicity and its laboratory measurements, summarise hydroxyurea‐associated data from both preclinical and clinical studies, and discuss carcinogenic potential. The genotoxicity results clearly demonstrate that hydroxyurea does not directly bind DNA and is not mutagenic. Rather, its genotoxic effects are limited to indirect clastogenicity occurring in select cell types, and only when high dose and time thresholds are exceeded. This absence of mutagenic activity is consistent with the observed lack of any compelling carcinogenic potential. Since hydroxyurea therapy for SCA carries minimal carcinogenic risks, the current drug labelling should be modified accordingly, and prescribing practices should be broadened to allow better access and increased utilisation of this highly effective drug.
Molecular dynamics of targeting CD38 in multiple myeloma
Authors: Malavasi Fabio , Faini Angelo C. , Morandi Fabio , Castella Barbara , Incarnato Danny , Oliviero Salvatore , Horenstein Alberto L. , Massaia Massimo , van de Donk Niels W. C. J. , Richardson Paul G.
Published: February 2021

Multiple functions of CD38 need exploring to expand clinical application of anti‐CD38 antibodies in multiple myeloma (MM). We investigated membrane dynamics of MM cells and subsequent events when CD38 is targeted by therapeutic antibodies. Human MM cells (BF01) were co‐cultured in vitro with therapeutic antibody (or control immunoglobulin G) and analysed using gene expression profiling. Microvesicles from antibody‐exposed cells were analysed for differential gene and microRNA (miRNA) expression, and for phenotypic characterisation. Exposure of BF01 cells to anti‐CD38 antibody resulted in CD38 membrane redistribution, upregulation of metabolism‐related genes and downregulation of genes involved in cell cycle processes. Microvesicles derived from antibody‐exposed cells showed increased CD73 and CD39 expression, presence of programmed death‐ligand 1 and significant up‐/down‐modulation of miRNAs. Microvesicles accumulated around immunoglobulin Fc receptor‐positive (FcR+) cells. Upon internalisation, natural killer cells displayed significantly increased expression of genes related to activation and immune response, and downregulation of genes involved in the cell cycle. Cells may use microvesicles to transmit signals distally as part of a survival strategy. Microvesicles are equipped on their surface with enzymatic machinery leading to production of tolerogenic adenosine. Further, they are internalised in FcR+ cells with significant functional modifications. These observations have relevance for improving anti‐CD38 therapeutic antibodies through targeting this mechanism and its sequelae.
Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population‐based study
Authors: da Cunha‐Bang Caspar , Rostgaard Klaus , Andersen Michael A. , Rotbain Emelie C. , Grønbæk Kirsten , Frederiksen Henrik , Niemann Carsten U. , Hjalgrim Henrik
Published: February 2021

Patients with chronic lymphocytic leukaemia (CLL) have an increased risk of new malignancies. However, limited data have been published about the impact of CLL treatment on this risk. Here we followed a Danish population‐based cohort of CLL patients for risks of new malignancies. Patients in the Danish CLL registry (2008–2017) were included. Up to 50 CLL‐free matched comparators were identified. First‐line treatment was categorized into four groups; bendamustine, chlorambucil, fludarabine or other. Patients were followed from CLL diagnosis for individual types of malignancy. Adjusted hazard ratios (HR) for new malignancies and 95% confidence intervals (95% CI) were calculated. Overall, 4286 CLL patients and 214 150 controls developed 594 and 20 565 new malignancies respectively. Risk of new malignancies was increased for CLL patients. Chemotherapy treatment was registered for 1064 (25%) patients with CLL. Chemotherapy was associated with increased HR (1·51, 95% CI: 1·3–1·8) of any new malignancy. Specifically, fludarabine was associated with an increased risk of myelodysplastic syndrome (MDS) (HR 4·93, 95% CI: 1·2–19·8). Patients with CLL are at increased risk of other haematological and solid malignancies compared to the general population. Chemotherapy exposure is associated with increased risk of second malignancies and fludarabine is associated with increased risk of MDS.
Cognitive performance as a predictor of healthcare transition in sickle cell disease
Authors: Saulsberry‐Abate Anjelica C. , Partanen Marita , Porter Jerlym S. , Podila Pradeep S. B. , Hodges Jason R. , King Allison A. , Wang Winfred C. , Schreiber Jane E. , Zhao Xiwen , Kang Guolian , Jacola Lisa M. , Hankins Jane S.
Published: February 2021

Neurocognitive deficits in sickle cell disease (SCD) may impair adult care engagement. We investigated the relationship between neurocognitive functioning and socio‐environmental factors with healthcare transition outcomes. Adolescents aged 15–18 years who had neurocognitive testing and completed a visit with an adult provider were included. Transition outcomes included transfer interval from paediatric to adult care and retention in adult care at 12 and 24 months. Eighty adolescents (59% male, 64% HbSS/HbSβ0‐thalassaemia) were included. Mean age at adult care transfer was 18·0 (±0·3) years and transfer interval was 2·0 (±2·3) months. Higher IQ (P = 0·02; PFDR = 0·05) and higher verbal comprehension (P = 0·008; PFDR = 0·024) were associated with <2 and <6 month transfer intervals respectively. Better performance on measures of attention was associated with higher adult care retention at 12 and 24 months (P = 0·009; PFDR = 0·05 and P = 0·04; PFDR = 0·12 respectively). Transfer intervals <6 months were associated with smaller households (P = 0·02; PFDR = 0·06) and households with fewer children (P = 0·02; PFDR = 0·06). Having a working parent was associated with less retention in adult care at 12 and 24 months (P = 0·01; P = 0·02 respectively). Lower IQ, verbal comprehension, attention difficulties and environmental factors may negatively impact transition outcomes. Neurocognitive function should be considered in transition planning for youth with SCD.
Identity and action: Help‐seeking requests in calls to a victim support service
Authors: Tennent Emma
Published: February 2021

The nature of the link between identity and action is a fundamental question for social science. One focus in psychology is how actions like seeking help are implicated in matters of identity. This paper presents a discursive psychology study of identity and help in social interaction. Drawing on a corpus of nearly 400 recorded calls to a victim support helpline, I analysed how participants oriented to the link between identity and help. With attention to epistemic, deontic, and affective relations between participants, I analysed how identity was demonstrably relevant and procedurally consequential for building and interpreting help‐seeking requests. Participants displayed an understanding that seeking help from Victim Support necessarily implicates identity. Callers’ identities as victims or clients rendered their help‐seeking accountable and invoked identities for call‐takers as representatives of a support service. The findings show that identity and help are mutually constitutive. Seeking help constituted callers’ identities as victims; and their identities as victims constituted their requests for help. I suggest that analysing identity and help in social interaction provides evidence for the mutually constitutive link between identity and action.
Automated and unbiased discrimination of ALS from control tissue at single cell resolution
Authors: Hagemann Cathleen , Tyzack Giulia E. , Taha Doaa M. , Devine Helen , Greensmith Linda , Newcombe Jia , Patani Rickie , Serio Andrea , Luisier Raphaëlle
Published: February 2021

Histopathological analysis of tissue sections is invaluable in neurodegeneration research. However, cell‐to‐cell variation in both the presence and severity of a given phenotype is a key limitation of this approach, reducing the signal to noise ratio and leaving unresolved the potential of single‐cell scoring for a given disease attribute. Here, we tested different machine learning methods to analyse high‐content microscopy measurements of hundreds of motor neurons (MNs) from amyotrophic lateral sclerosis (ALS) post‐mortem tissue sections. Furthermore, we automated the identification of phenotypically distinct MN subpopulations in VCP‐ and SOD1‐mutant transgenic mice, revealing common morphological cellular phenotypes. Additionally we established scoring metrics to rank cells and tissue samples for both disease probability and severity. By adapting this paradigm to human post‐mortem tissue, we validated our core finding that morphological descriptors robustly discriminate ALS from control healthy tissue at single cell resolution. Determining disease presence, severity and unbiased phenotypes at single cell resolution might prove transformational in our understanding of ALS and neurodegeneration more broadly.
Ependymoma‐like tumor with mesenchymal differentiation harboring C11orf95‐NCOA1/2 or ‐RELA fusion: A hitherto unclassified tumor related to ependymoma
Authors: Tomomasa Ran , Arai Yasuhito , Kawabata‐Iwakawa Reika , Fukuoka Kohei , Nakano Yoshiko , Hama Natsuko , Nakata Satoshi , Suzuki Nozomi , Ishi Yukitomo , Tanaka Shinya , Takahashi Jun A. , Yuba Yoshiaki , Shiota Mitsutaka , Natsume Atsushi , Kurimoto Michihiro , Shiba Yoshiki , Aoki Mikiko , Nabeshima Kazuki , Enomoto Toshiyuki , Inoue Tooru , Fujimura Junya , Kondo Akihide , Yao Takashi , Okura Naoki , Hirose Takanori , Sasaki Atsushi , Nishiyama Masahiko , Ichimura Koichi , Shibata Tatsuhiro , Hirato Junko , Yokoo Hideaki , Nobusawa Sumihito
Published: February 2021

Recurrent fusion genes involving C11orf95, C11orf95‐RELA, have been identified only in supratentorial ependymomas among primary CNS tumors. Here, we report hitherto histopathologically unclassifiable high‐grade tumors, under the tentative label of “ependymoma‐like tumors with mesenchymal differentiation (ELTMDs),” harboring C11orf95‐NCOA1/2 or ‐RELA fusion. We examined the clinicopathological and molecular features in five cases of ELTMDs. Except for one adult case (50 years old), all cases were in children ranging from 1 to 2.5 years old. All patients presented with a mass lesion in the cerebral hemisphere. Histologically, all cases demonstrated a similar histology with a mixture of components. The major components were embryonal‐appearing components forming well‐delineated tumor cell nests composed of small uniform cells with high proliferative activity, and spindle‐cell mesenchymal components with a low‐ to high‐grade sarcoma‐like appearance. The embryonal‐appearing components exhibited minimal ependymal differentiation including a characteristic EMA positivity and tubular structures, but histologically did not fit with ependymoma because they lacked perivascular pseudorosettes, a histological hallmark of ependymoma, formed well‐delineated nests, and had diffuse and strong staining for CAM5.2. Molecular analysis identified C11orf95‐NCOA1, ‐NCOA2, and ‐RELA in two, one, and two cases, respectively. t‐distributed stochastic neighbor embedding analysis of DNA methylation data from two cases with C11orf95‐NCOA1 or ‐NCOA2 and a reference set of 380 CNS tumors revealed that these two cases were clustered together and were distinct from all subgroups of ependymomas. In conclusion, although ELTMDs exhibited morphological and genetic associations with supratentorial ependymoma with C11orf95‐RELA, they cannot be regarded as ependymoma. Further analyses of more cases are needed to clarify their differences and similarities.
The formation of the Sichuan Basin, South China, during the Late Ediacaran to Early Cambrian
Authors: Gu Zhidong , Lonergan Lidia , Zhai Xiufen , Zhang Baomin , Lu Weihua
Published: February 2021

The Upper Ediacaran to Lower Cambrian of the Sichuan Basin in South China has long been considered to be dominated by shallow‐water deposition. Hydrocarbon exploration, however, has revealed that a NW‐SE trending intraplatform trough formed in the basin during the same period. Although different models have been proposed, the formation and evolution of the trough are still not fully understood. In this study, we investigate both the origin of the intraplatform trough and the formation of the Sichuan Basin by integrating seismic interpretation, well correlation and tectonic subsidence analysis. The seismic and well data clearly show three stages of development of the trough. The first stage, in the early Late Ediacaran, is characterized by considerable thinning of the lower two members of the Upper Ediacaran from the platform margins to the trough. In the second stage, in the late Late Ediacaran, the platform margins backstepped and the extent of the trough expanded significantly to a width of ca. ~400 km. The third stage, in the early Early Cambrian, was dominated by gradual filling of the trough and onlapping of the platform margins. Backstripped tectonic subsidence curves show one, or two closely spaced episodes of linear subsidence starting at ~550 Ma and then decreasing exponentially until ~450 Ma. The shape of the subsidence curves is consistent with formation of the Sichuan Basin by low, and slow amounts of lithospheric stretching of thickened cratonic lithosphere. The tectonic subsidence increases from the centre to the NW of the basin. Interestingly the margins of the trough do not correlate with contoured values of increased tectonic subsidence and we infer that the trough was a palaeogeographic embayment in a large carbonate platform that developed in a broad, ramp‐like area of slow and low subsidence tilting down to the proto‐Tethyan ocean located to the NW of the basin.
Prophylactic antiviral therapy for hepatitis B virus surface antigen‐positive patients with diffuse large B‐cell lymphoma treated with rituximab‐containing chemotherapy
Authors: Yamauchi Nobuhiko , Maruyama Dai , Choi Ilseung , Atsuta Yoshiko , Sakai Rika , Miyashita Kazuho , Moriuchi Yukiyoshi , Tsujimura Hideki , Kubota Nobuko , Yamamoto Go , Igarashi Tadahiko , Izutsu Koji , Yoshida Shinichiro , Kojima Kensuke , Uchida Toshiki , Inoue Yoshiko , Tsukamoto Norifumi , Ohtsuka Eiichi , Suzuki Sachiko , Inaguma Yoko , Ichikawa Satoshi , Gomyo Hiroshi , Ushijima Yoko , Nosaka Kisato , Kurata Mio , Tanaka Yasuhito , Ueda Ryuzo , Mizokami Masashi , Kusumoto Shigeru
Published: February 2021

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)‐positive patients with diffuse large B‐cell lymphoma (DLBCL) and 278 HBsAg‐negative patients with DLBCL, as a control cohort, who received rituximab‐containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation‐related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg‐positive patients were divided into three groups based on anti–HBV prophylactic therapy: no nucleos(t)ide analogue (non–NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4‐year cumulative incidence (CI) of hepatitis in HBsAg‐positive and HBsAg‐negative patients was 21.1% and 14.6% (P = .081), respectively. The 4‐year CI of HBV reactivation‐related hepatitis was higher in HBsAg‐positive patients than in HBsAg‐negative patients (8.0% vs 0.4%; P < .001). Among HBsAg‐positive patients, the 4‐year CI of HBV reactivation‐related hepatitis was the highest in the non–NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non–NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation‐related hepatitis and mortality in HBsAg‐positive DLBCL patients receiving rituximab‐containing chemotherapy.