bluuebunny/crossref_metadata_2025 huggingface dataset:
Serologic and molecular studies to identify neonatal alloimmune neutropenia in a cohort of 10,000 neonates
Authors: Abbas Samira A. , Lopes Larissa B. , Moritz Elyse , Martins Juliana O. , Chiba Akemi K , Kunioshi Alessandra M. , Barbosa Elisama S. , Langhi Junior Dante M. , dos Santos Amélia M. N. , Godinho Cárlei H. , Bordin José O.
Published: February 2021

Neonatal alloimmune neutropenia (NAIN) is caused by maternal alloimmunisation to fetal human neutrophil antigens (HNAs). This study investigated maternal HNA/HLA alloantibodies involved with NAIN and identified the frequency of NAIN in Brazilian neonates. Neonatal neutropenia (neutrophil count < 1.5 × 109/L) was investigated in samples from 10,000 unselected neonates, resulting in 88 neutropenic newborns (NBs) and their 83 mothers. Genotyping was performed by PCR‐SSP (HNA‐1/‐4) and PCR‐RFLP (HNA‐3/‐5). Serologic studies were performed by GAT (granulocyte agglutination test), Flow‐WIFT (white blood cells immunofluorescence test) and LABScreen‐Multi‐HNA‐Kit (OneLambda®) (LSM). Neonatal neutropenia was identified in 88/10,000 (0·9%) NBs. Genotyping revealed 60·2% maternal‐fetal HNA incompatibilities (31·8% for HNA‐1; 14·8% for HNA‐3; 15·9% for HNA‐4; 21·6% for HNA‐5). Serologic studies revealed 37·3% of mothers with positive results with at least one technique. The detected anti‐HNA specificities were confirmed in eight positive cases related to HNA‐1/‐3 systems. In cases with maternal‐fetal HNA‐4/‐5 incompatibility, no specific neutrophil alloantibodies were found but anti‐HLA I/II were present. Anti‐HNA‐2 was not identified. This is a large Brazilian study which involved the investigation of antibodies against all five HNA systems in neutropenia cases and showed a frequency of NAIN in 8/10,000 neonates. Among the HNA antibodies identified, we highlight the anti‐HNA‐1d and anti‐HNA‐3b, antibodies unusual in alloimmunised women, and rarely related to NAIN cases.
Cord blood beyond transplantation: can we use the experience to advance all cell therapies?
Authors: Scaradavou Andromachi
Published: February 2021

Unrelated cord blood (CB) units, already manufactured, fully tested and stored, are high‐quality products for haematopoietic stem cell transplantation and cell therapies, as well as an optimal starting material for cell expansion, cell engineering or cell re‐programming technologies. CB banks have been pioneers in the development and implementation of Current Good Manufacturing Practices for cell‐therapy products. Sharing their technological and regulatory experience will help advance all cell therapies, CB‐derived or not, particularly as they transition from autologous, individually manufactured products to stored, ‘off‐the shelf’ treatments. Such strategies will allow broader patient access and wide product utilisation.
Non‐myeloablative human leukocyte antigen‐matched related donor transplantation in sickle cell disease: outcomes from three independent centres
Authors: Alzahrani Mohsen , Damlaj Moussab , Jeffries Neal , Alahmari Bader , Singh Avani , Rondelli Damiano , Tisdale John F. , Saraf Santosh L. , Hsieh Matthew M.
Published: February 2021

Non‐myeloablative haematopoietic progenitor cell transplantation (HPCT) from matched related donors (MRD) has been increasingly utilized in sickle cell disease (SCD). A total of 122 patients received 300 cGy of total body irradiation (TBI), alemtuzumab, unmanipulated filgrastim‐mobilized peripheral blood HPC and sirolimus. The median follow‐up was four years; median age at HPCT was 29 years. Median neutrophil and platelet engraftment occurred on day 22 and 19 respectively; 41 patients required no platelet transfusions. Overall and sickle‐free survival at one and five years were 93% and 85% respectively. Age, sex, pre‐HPCT sickle complications, ferritin and infused HPC numbers were similar between graft failure and engrafted patients. Mean donor myeloid chimaerism at one and five years post HPCT were 84% and 88%, and CD3 was 48% and 53% respectively. Two patients developed grade 1 and 2 skin graft‐versus‐host disease (GVHD) with no chronic GVHD. Median days of recipients taking immunosuppression were 489; 83% of engrafted patients have discontinued immunosuppression. Haemoglobin, haemolytic parameters and hepatic iron levels improved post HPCT. Pulmonary function testing, hepatic histology and neurovascular imaging remained stable, suggesting cessation of further sickle‐related injury. Fourteen patients had children. In this largest group of adult SCD patients, this regimen was highly efficacious, well‐tolerated despite compromised organ functions pre HPCT, and without clinically significant GVHD.
‘You can’t bullshit a bullshitter’ (or can you?): Bullshitting frequency predicts receptivity to various types of misleading information
Authors: Littrell Shane , Risko Evan F. , Fugelsang Jonathan A.
Published: February 2021

Research into both receptivity to falling for bullshit and the propensity to produce it have recently emerged as active, independent areas of inquiry into the spread of misleading information. However, it remains unclear whether those who frequently produce bullshit are inoculated from its influence. For example, both bullshit receptivity and bullshitting frequency are negatively related to cognitive ability and aspects of analytic thinking style, suggesting that those who frequently engage in bullshitting may be more likely to fall for bullshit. However, separate research suggests that individuals who frequently engage in deception are better at detecting it, thus leading to the possibility that frequent bullshitters may be less likely to fall for bullshit. Here, we present three studies (N = 826) attempting to distinguish between these competing hypotheses, finding that frequency of persuasive bullshitting (i.e., bullshitting intended to impress or persuade others) positively predicts susceptibility to various types of misleading information and that this association is robust to individual differences in cognitive ability and analytic cognitive style.
Defining prostate cancer size and treatment margin for focal therapy: does intralesional heterogeneity impact the performance of multiparametric MRI?
Authors: Aslim Edwin Jonathan , Law Yu Xi Terence , Fook‐Chong Stephanie Man Chung , Ho Henry Sun Sien , Yuen John Shyi Peng , Lau Weber Kam On , Lee Lui Shiong , Cheng Christopher Wai Sam , Ngo Nye Thane , Law Yan Mee , Tay Kae Jack
Published: February 2021

Objectives

To evaluate the impact of intralesional heterogeneity on the performance of multiparametric magnetic resonance imaging (mpMRI) in determining cancer extent and treatment margins for focal therapy (FT) of prostate cancer.

Patients and Methods

We identified men who underwent primary radical prostatectomy for organ‐ confined prostate cancer over a 3‐year period. Cancer foci on whole‐mount histology were marked out, coding low‐grade (LG; Gleason 3) and high‐grade (HG; Gleason 4–5) components separately. Measurements of entire tumours were grouped according to intralesional proportion of HG cancer: 0%, <50% and ≥50%; the readings were corrected for specimen shrinkage and correlated with matching lesions on mpMRI. Separate measurements were also taken of HG cancer components only, and correlated against entire lesions on mpMRI. Size discrepancies were used to derive the optimal tumour size and treatment margins for FT.

Results

There were 122 MRI‐detected cancer lesions in 70 men. The mean linear specimen shrinkage was 8.4%. The overall correlation between histology and MRI dimensions was r = 0.79 (P < 0.001). Size correlation was superior for tumours with high burden (≥50%) compared to low burden (<50%) of HG cancer (r = 0.84 vs r = 0.63; P = 0.007). Size underestimation by mpMRI was more likely for larger tumours (51% for >12 mm vs 26% for ≤12 mm) and those containing HG cancer (44%, vs 20% for LG only). Size discrepancy analysis suggests an optimal tumour size of ≤12 mm and treatment margins of 5–6 mm for FT. For tumours ≤12 mm in diameter, applying 5‐ and 6‐mm treatment margins would achieve 98.6% and 100% complete tumour ablation, respectively. For tumours of all sizes, using the same margins would ablate >95% of the HG cancer components.

Conclusions

Multiparametric MRI performance in estimating prostate cancer size, and consequently the treatment margin for FT, is impacted by tumour size and the intralesional heterogeneity of cancer grades.
Supporting food security for Indigenous families through the restoration of Indigenous foodways
Authors: Richmond Chantelle , Kerr Rachel Bezner , Neufeld Hannah , Steckley Marylynn , Wilson Kathi , Dokis Brian
Published: February 2021

Indigenous families are overrepresented among those within Canada who experience food insecurity. Studies have largely focused on northern populations, with less attention paid to southern and urban communities, including the social, cultural, and geographic processes that challenge food security. In this study, we present findings from a decade‐long community‐based study with the Southwest Ontario Aboriginal Health Access Centre (London, Ontario) to examine family perspectives related to the social determinants of food security. These topics were explored through qualitative interviews (n  = 25) and focus groups (n = 2) with First Nation mothers with young children from the city of London, and a nearby reserve community. Interviewees from both geographies identified a number of socio‐economic challenges including household income and transportation. However, some interviewees also shed light on barriers to healthy eating unique to these Indigenous contexts including access issues such as a lack of grocery stores on‐reserve; loss of knowledge related to the utilization of traditional foods; and the erosion of community, familial, and social supports. Resolving these unique determinants of food security for urban and reserve‐based First Nation families will require a range of economic and culturally specific interventions, particularly those that support development and uptake of Indigenous foodways.
Anti‐tumor efficacy of human anti‐c‐met CAR‐T cells against papillary renal cell carcinoma in an orthotopic model
Authors: Mori Jun‐ich , Adachi Keishi , Sakoda Yukimi , Sasaki Takahiro , Goto Shunsuke , Matsumoto Hiroaki , Nagashima Yoji , Matsuyama Hideyasu , Tamada Koji
Published: February 2021

Chimeric antigen receptor (CAR)‐T cell therapy has shown salient efficacy in cancer immunotherapy, particularly in the treatment of B cell malignancies. However, the efficacy of CAR‐T for solid tumors remains inadequate. In this study, we displayed that c‐met is an appropriate therapeutic target for papillary renal cell carcinoma (PRCC) using clinical samples, developed an anti‐human c‐met CAR‐T cells, and investigated the anti‐tumor efficacy of the CAR‐T cells using an orthotopic mouse model as pre‐clinical research. Administration of the anti‐c‐met CAR‐T cells induced marked infiltration of the CAR‐T cells into the tumor tissue and unambiguous suppression of tumor growth. Furthermore, in combination with axitinib, the anti‐tumor efficacy of the CAR‐T cells was synergistically augmented. Taken together, our current study demonstrated the potential for clinical application of anti‐c‐met CAR‐T cells in the treatment of patients with PRCC.
Developmental Improvements and Persisting Difficulties in Children’s Metacognitive Monitoring and Control Skills: Cross‐Sectional and Longitudinal Perspectives
Authors: Bayard Natalie S. , van Loon Mariëtte H. , Steiner Martina , Roebers Claudia M.
Published: February 2021

This study investigated age‐dependent improvements of monitoring and control in 7/8‐ and 9/10‐year‐old children. We addressed prospective (judgments of learning and restudy selections) and retrospective metacognitive skills (confidence judgments and withdrawal of answers). Children (N = 305) completed a paired‐associate learning task twice, with a 1‐year delay. Results revealed improvements in retrospective, but not in prospective monitoring and control. Furthermore, control remained suboptimal, seemingly a consequence of overoptimistic monitoring. Both age groups showed stronger monitoring‐based control at the second compared to the first assessment. The comparison with a cross‐sectional sample (N = 144) revealed that improvements in retrospective monitoring can be mainly attributed to naturally occurring development, whereas retrospective control seemed to improve due to increased task familiarity.
Comparison of peri‐implant clinical outcomes of digitally customized and prefabricated abutments: A systematic review and meta‐analysis
Authors: Raee Amir , Alikhasi Marzieh , Nowzari Hessam , Djalalinia Shirin , Khoshkam Vahid , Moslemi Neda
Published: February 2021

Background

Digitally customized abutments are increasingly used in contemporary implant prosthodontics.

Purpose

This systematic review and meta‐analysis aimed at comparing the peri‐implant clinical outcomes of digitally customized and prefabricated abutments.

Materials and methods

The search strategies included electronic databases (PubMed, Embase, Scopus, and Cochrane clinical trials database) and related journals up to September, 2020. A qualitative and quantitative synthesis was performed on data extracted from the included studies.

Results

Three RCTs (number of patients = 120; number of dental implants = 120) and two prospective cohort studies (number of patients = 144; number of dental implants = 144) with one to three‐year follow‐up periods were included. The quantitative analyses did not demonstrate a significant difference between digitally customized and prefabricated abutments for peri‐implant pocket depth (P = 0.62), plaque index (P = 0.67), bleeding on probing (P = 0.43), keratinized mucosa width (P = 0.75), and pink aesthetic score (P = 0.30) at one‐year follow‐up visit. The qualitative analyses for marginal bone level change, calculus accumulation, implant survival rate, implant success rate, white aesthetic score, and patient‐reported outcomes did not demonstrate a significant difference between two groups during 1 to 3‐year follow‐up visits.

Conclusion

The current data do not provide evidence of significant differences between two abutment fabrication methods in terms of peri‐implant clinical outcomes within short‐term period (CRD42020170807).
Customized CAD/CAM titanium meshes for the guided bone regeneration of severe alveolar ridge defects: Preliminary results of a retrospective clinical study in humans
Authors: Chiapasco Matteo , Casentini Paolo , Tommasato Grazia , Dellavia Claudia , Del Fabbro Massimo
Published: February 2021

Objectives

To present the results of guided bone regeneration (GBR) of atrophic edentulous ridges with customized CAD/CAM titanium meshes.

Material and methods

Forty‐one patients, presenting with 53 atrophic sites, were enrolled between 2018 and 2019. GBR was obtained with titanium meshes filled with autogenous bone chips and bovine bone mineral (BBM). After a mean of 7 months (range: 5–12 months), meshes were removed and 106 implants placed. After a mean of 3.5 months (range: 2–5 months), implants were uncovered and prosthetic restorations started. The outcomes were vertical and horizontal bone augmentation changes, biological complications and implant survival.

Results

Out of 53 sites, 11 underwent mesh exposure: eight of them were followed by uneventful integration of the graft, while three by partial bone loss. The mean vertical and horizontal bone gain after reconstruction was 4.78 ± 1.88 mm (range 1.00–8.90 mm) and 6.35 ± 2.10 mm (range 2.14–11.48 mm), respectively. At the time of implant placement, mean changes of initial bone gain were −0.39 ± 0.64 mm (range −3.1 to + 0.80 mm) and −0.49 ± 0.83 mm (range –3.7 to +0.4 mm), in the vertical and horizontal dimensions, respectively. Reduction of bone volume was significantly higher (p < .001 for both dimensions) in the exposed sites. The mean follow‐up of implants after loading was 10.6 ± 6.5 months (range: 2–26 months). The survival rate of implants was 100%.

Conclusion

Customized titanium meshes can represent a reliable tool for GBR of severely atrophic sites, with simplification of the surgical phases.
Need for lateral bone augmentation at two narrow‐diameter implants: A prospective, controlled, clinical study
Authors: Roccuzzo Andrea , Imber Jean‐Claude , Jensen Simon Storgård
Published: February 2021

Objectives

To detect the potential influence of implant diameter and anatomic factors on the need for bone augmentation procedures (BAPs) when replacing congenitally missing lateral incisors (MLIs).

Materials and methods

Patients with congenitally missing MLIs with a mesio‐distal distance between the canine and the central incisor of 5.9–6.3 mm received a Ø2.9 mm implant while Ø3.3 mm implants were placed when the distance was 6.4–7.1 mm. The following linear measurements were recorded using a calliper: width of the alveolar process (WAP), width of the bony alveolar ridge (WAR) and thickness of the facial bone after implant osteotomy (TFB). Guided bone regeneration was performed in case of fenestration‐ or dehiscence‐type defects or a thin TFB (<1.7 mm).

Results

Fifty Ø2.9 mm and 50 Ø3.3 mm were included in 100 patients. WAP and WAR did not differ between the groups (p > .05). TFB was statistically significant larger in the Ø2.9 group (1.75 ± 0.59 mm) compared to the Ø3.3 group (1.5 ± 0.63 mm) (p = .041). Fenestration‐type defects (p = .005) and a thin facial bone wall (p = .045) was observed more frequently in the Ø3.3 compared to the Ø2.9 group. Correspondingly, BAP was indicated more frequently in the Ø3.3 compared to the Ø2.9 group (p = .017). WAP, MD and WAR were statistically significant correlated to the need for BAP (p < .001). As independent variable, only WAR influenced the probability of BAP (p < .001).

Conclusion

The use of 2.9 diameter implants was correlated to a reduced frequency of BAP compared to 3.3 mm implants, without reaching a statistically significant difference. Measurement of the WAP provides the clinician useful information to predict BAP.
Objective measurement and patient‐reported evaluation of the nasal airway: Is correlation dependent on symptoms or on nasal airflow?
Authors: Xavier Rui , Azeredo‐Lopes Sofia , Menger Dirk‐Jan , de Carvalho Henrique Cyrne , Spratley Jorge
Published: February 2021

Background

Evidence has shown that the sensation of nasal breathing is related to variations in nasal mucosa temperature produced by airflow. An appropriate nasal airflow is necessary for changing mucosal temperature. Therefore, the correlation between objective measurements of nasal airflow and patient‐reported evaluation of nasal breathing should be dependent on the level of nasal airflow.

Objectives

To find if the correlation between patient‐reported assessment of nasal breathing and objective measurement of nasal airflow is dependent on the severity of symptoms of nasal obstruction or on the level of nasal airflow.

Methods

The airway of 79 patients was evaluated using NOSE score and peak nasal inspiratory flow (PNIF). Three subgroups were created based on NOSE and three subgroups were created based on PNIF level to find if correlation was dependent on nasal symptoms or airflow.

Results

The mean value of PNIF for the 79 patients was 92.6 L/min (SD 28.1 L/min). The mean NOSE score was 48.4 (SD 24.4). The correlation between PNIF and NOSE was statistically significant (P = .03), but with a weak association between the two variables (r = −.248).

Evaluation of correlation based on symptoms demonstrated a weak or very weak association in each subgroup (r = −.250, r = −.007, r = −.104). Evaluation of correlation based on nasal airflow demonstrated a very weak association for the subgroups with middle‐level and high PNIF values (r = −.190, r = −.014), but a moderate association for the subgroup with low PNIF values (r = −.404).

Conclusions

This study demonstrated a weak correlation between NOSE scores and PNIF values in patients non‐selected according to symptoms of nasal obstruction or to airflow. It demonstrated that patients with symptoms of nasal obstruction have different levels of nasal airflow and that low nasal airflow prevents the sensation of good nasal breathing. Therefore, patients with symptoms of nasal obstruction may require improving nasal airflow to improve nasal breathing sensation.
Frequency of sensitization to the individual fragrances of fragrance mix I and II according to the factors included in the MOAHLFA index
Authors: Sánchez‐Pujol María J. , Docampo‐Simón Alexandre , Mercader Pedro , González‐Pérez Ricardo , Hervella‐Garcés Marcos , Sanz‐Sánchez Tatiana , Córdoba Susana , Sánchez‐Pérez Javier , Heras‐Mendaza Felipe , Giménez‐Arnau Ana M. , Gatica‐Ortega María E. , Pastor‐Nieto María A. , Zaragoza Violeta , Carrascosa José M. , García‐Bravo Begoña , Ruiz‐González Inmaculada , Borrego Leopoldo , Sánchez‐Pedreño Paloma , de Frutos Javier O. , Armario‐Hita José C. , García‐Gavín Juan , Fernández‐Redondo Virginia , Serra Esther , Silvestre Juan F.
Published: February 2021

Background

Fragrances constitute the second most frequent cause of allergic contact dermatitis in Spain.

Objectives

To determine the rate of sensitization to the individual fragrances of fragrance mix (FM) I and FM II for each of the demographic and clinical factors included in the MOAHLFA (male, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, age) index.

Methods

We conducted a 5‐year retrospective study in 23 Spanish centres. We identified the patients who had undergone patch testing with a specific fragrance series after reacting positively to fragrance markers in a baseline series. We obtained the MOAHLFA index items in this population, then calculated for each demographic and clinical factor the frequencies of sensitization to the individual fragrances of FM I and FM II.

Results

A specific fragrance series was patch tested in 1013 patients. The most frequent allergens in men, women, children, and retired people were Evernia prunastri (16%), geraniol (16.6%), isoeugenol (17.9%), and geraniol (22.4%), respectively. Citral (20.5%) and hydroxyisohexyl 3‐cyclohexene carboxaldehyde (HICC) (14.5%) were the most common allergens in occupational eczemas and were also associated with a large proportion of hand and facial dermatitis.

Conclusions

Frequency of sensitization to the individual fragrances of FM I and FM II varies with age, sex, affected body region, and history of occupational or atopic dermatitis.
A scoring system to predict a prolonged length of stay after surgery for Crohn’s disease
Authors: Wickramasinghe Dakshitha , Adegbola Samuel , Sahnan Kapil , Morar Pritesh , Carvello Michele , Di Candido Francesca , Maroli Annalisa , Spinelli Antonino , Warusavitarne Janindra
Published: February 2021

Aim

Many factors influence the postoperative length of stay (LOS) in Crohn's disease (CD). This study aims to identify the factors associated with a prolonged LOS after ileocolic resection (ICR) for CD and to develop a scoring system to predict the postoperative LOS in CD.

Method

Patient data were collected from St Marks Hospital, London, UK, and the Humanitas Clinical and Research Center Milan, Italy, for all patients who underwent an ICR for CD from 2005 to 2017. Logistic regression was used for multivariate analysis. The scoring system was developed from the logistic regression model. The performance of the scoring system was evaluated using the area under the receiver operating characteristic curve (AUROC).

Results

A total of 628 surgeries were included in the analysis. Eighty eight surgeries were excluded due to missing data. The remaining 543 were divided into two cohorts for the development (n = 418) and validation (n = 125) of the scoring system. The regression model was statistically significant (p < 0.0001). The statistically significant independent variables included the time since diagnosis, American Society of Anesthesiologists (ASA) grade, perioperative use of steroids, surgical access, strictureplasty and platelet count. The AUROCs for the development and validation cohorts were 0.732 and 0.7, respectively (p < 0.0001). The cut‐off score suggested by Youden's index was 50, with a sensitivity of 65.6% and a specificity of 73.3%.

Conclusion

The time since diagnosis, ASA grade, steroid use, surgical access, strictureplasty and platelet count were associated with a prolonged LOS and were used to develop a scoring system. The calculator is available online at https://rebrand.ly/Crohnscal.
A wolf in fox's clothing? Using stable isotopes to quantify ecological replacement
Authors: Clark T. J. , Vick Bugge , Newton Jason , Marengo Ilaria , Wakefield Ewan D.
Published: February 2021

Ecological replacement as a conservation tool presupposes that nonnative taxa can restore degraded ecosystems by performing the ecological functions of extinct taxa. This assumption is rarely tested however, largely because it is difficult to quantify the functions of species extirpated long ago. Here, we test whether feral South American grey foxes (SAGF), introduced to the Falkland Islands ∼90 years ago, act as unintended ecological replacements for endemic Falkland Islands wolves (FIW), extirpated during the 19th century. Using hair stable isotope ratios as proxies for diet, we show that the isotopic niche space of modern SAGFs almost completely encompasses that of archaic FIWs. However, the former's niche is larger so while SAGFs may play similar ecological roles to FIWs, they probably perform additional functions, which may or may not be desirable. In so doing, we illustrate a generalized framework for using comparative isotopic niche analysis to test for ecological replacement objectively.
Single‐cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics
Authors: Li Yan , Liu Yaxiao , Gao Zhengdong , Zhang Lekai , Chen Lipeng , Wu Zonglong , Liu Qinggang , Wang Shuai , Zhou Nan , Chai Toby C. , Shi Benkang
Published: February 2021

Objectives

Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single‐cell RNA sequencing to thoroughly characterize mouse bladder urothelium.

Materials and methods

A total of 18,917 single cells from mouse bladder urothelium were analysed by unbiased single‐cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infection models.

Results

Unsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal‐like cells labelled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM+ urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome–regulating genes were found differentially expressed among different urothelial cell subpopulations.

Conclusions

Our study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.
Discordance between immunofluorescence and immunohistochemistry C4d staining and outcomes following heart transplantation
Authors: Fujino Takeo , Kumai Yuto , Yang Benjamin , Kalantari Sara , Rodgers Daniel , Henriksen Kammi , Chang Anthony , Husain Aliya , Kim Gene , Sayer Gabriel , Uriel Nir
Published: February 2021

Background

Capillary deposition of C4d is an important marker of antibody‐mediated rejection (AMR) following heart transplantation (HT). There are two immunopathologic assay methods for detecting C4d: frozen‐tissue immunofluorescence (IF) and paraffin immunohistochemistry (IHC). The clinical significance of discrepancy between the results of IF and IHC has not been understood.

Methods and results

We reviewed 2187 biopsies from 142 HT recipients who had biopsies with assessment of both IF and IHC staining. Among them, 103 (73%) patients had negative IF and IHC C4d staining (Negative Group) and 32 (23%) patients had positive IF but negative IHC staining (Discordant Group). At the time of positive biopsy, 6 (19%) Discordant patients had graft dysfunction, compared to 5 (5%) Negative patients (p = .022). Cumulative incidence of cellular rejection at 1 year was comparable (31% vs. 29%, p = .46); however, cumulative incidence of AMR was significantly higher in the Discordant group (21% vs. 4%, p = .004). Overall 1‐year survival was comparable (90% vs. 96%, p = .24); however, freedom from heart failure (HF) was significantly lower in the Discordant group (70% vs. 96%, p < .001).

Conclusion

The Discordant group showed higher rates of graft dysfunction, AMR and HF admission than the Negative group.
Filaggrin expression via immunohistochemistry in basal cell carcinoma and squamous cell carcinoma
Authors: Vanderbeck Kaitlin , Orr Christine E. , Parvinnejad Nikoo , Wang Tao , Bradshaw Scott , Wang Ami , Asai Yuka
Published: February 2021

Background

Filaggrin is a protein integral to the structure and function of the epidermis. Filaggrin (FLG) loss‐of‐function (LOF) mutations are common and increase the risk of developing atopic dermatitis (AD) and ichthyosis vulgaris (IV). Epidemiologic data suggest a link between skin cancer and AD. We examined if FLG staining pattern can be used to characterize cutaneous squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and reactive squamous epithelium.

Methods

Tissue microarrays (TMAs) were created from 196 cases of formalin‐fixed paraffin‐embedded (FFPE) SCC and 144 BCC cases. TMAs and sections of reactive squamous epithelium were stained with optimized anti‐FLG antibody and evaluated for FLG expression (normal, abnormal, or negative).

Results

FLG was absent in poorly differentiated (PD) compared to well‐differentiated (WD) SCC (P < .0001) and moderately‐differentiated (MD) (P = .0231) SCC, and in MD compared to WD SCC (P = .0099). Abnormal staining was significantly increased in PD compared to WD cases (P = .0039) and in MD compared to WD cases (P = .0006). Most BCC did not exhibit FLG expression (P < .05). Reactive squamous epithelium demonstrated normal, but exaggerated FLG expression.

Conclusions

Our findings demonstrate the differences in FLG expression patterns in types of keratinocyte carcinomas and their mimickers.
eDNA‐based detection of a vulnerable crocodile newt (Tylototriton uyenoi) to influence government policy and raise public awareness
Authors: Osathanunkul Maslin , Minamoto Toshifumi
Published: February 2021

Aim

Although at least five Tylototriton species were recorded in Thailand, only Tylototriton verrucosus is registered as a protected species under the Wildlife Preservation and Protection Act in Thailand. Populations of T. uyenoi are now severely declining, caused by anthropogenic activities. As intense human pressure is having profound effects on the diminishment in T. uyenoi populations, a conservation plan is needed. Information such as the abundance and distribution of a species is necessary. Yet, current established survey methods are either time‐consuming or labour‐intensive. Here, eDNA‐based detection was developed for tracking the presence of the T. uyenoi.

Location

Thailand.

Methods

We target the surveillance of T. uyenoi using eDNA. Primers and a probe specific to T. uyenoi were designed and tested for their specificity and sensitivity. Water samples were collected once a month from August to January at three sites in Doi Suthep and at three extra sites within the range of the species. Three hundred ml samples of water were collected and filtered. Environmental DNA was extracted and then subjected to qPCR assay in an attempt to detect T. uyenoi.

Results

The qPCR assay was found to be species‐specific to T. uyenoi. Both PCR and qPCR did not result in any positive detection of three congeners or other non‐target species. The LOD and the LOQ of the assay were determined by an analysis of the standard curve, and it was found that the LOD and the LOQ were 7.99 and 9.0 copies per reaction, respectively. Environmental DNA was detected in water samples from all sites where T. uyenoi has been known to occur, but detection varied among sites and sampling times. In addition, low amounts of eDNA were detected in three sites with unknown occupancy of newts, but within the species’ range.

Conclusions

Our findings suggest that eDNA survey is a powerful tool for tracking T. uyenoi throughout the year regardless of the sampling site conditions. Similar to other amphibians, T. uyenoi is severely declining due to anthropogenic factors. In order to have an effective conservation plan, knowledge of a species’ distribution is needed. To our knowledge, this was the first study that used eDNA to track the crocodile newt in Thailand.
Precut fistulotomy using scissor‐type endoscopic submucosal dissection knife
Authors: Shibuya Hitoshi , Suzuki Sho , Takahashi Toshimi
Published: February 2021

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Cerebral visual impairment‐related vision problems in primary school children: a cross‐sectional survey
Authors: Williams Cathy , Pease Anna , Warnes Penny , Harrison Sean , Pilon Florine , Hyvarinen Lea , West Stephanie , Self Jay , Ferris John ,   CVI Prevalence Study Group
Published: February 2021

Aim

To estimate how many children in mainstream primary schools have cerebral visual impairment (CVI)‐related vision problems and to investigate whether some indicators might be useful as red flags, if they were associated with increased risk for these problems.

Method

We conducted a survey of primary school children aged 5 to 11 years, using whether they were getting extra educational help and/or teacher‐ and parent‐reported behaviour questionnaires to identify children at risk for CVI. These and a random 5% sample were assessed for CVI‐related vision problems. We compared the usefulness of potential red flags using likelihood ratios.

Results

We received questionnaires on 2298 mainstream‐educated children and examined 248 children (152 [61%] males, 96 females [39%]; mean age 8y 1mo, SD 20mo, range 5y 6mo–11y 8mo). We identified 78 out of 248 children (31.5% of those examined, 3.4% of the total sample), who had at least one CVI‐related vision problem. The majority (88%) were identified by one or more red flag but none were strongly predictive. Fewer than one in five children with any CVI‐related vision problem had reduced visual acuity.

Interpretation

Children with CVI‐related vision problems were more prevalent than has been appreciated. Assessment of at‐risk children may be useful so that opportunities to improve outcomes for children with CVI‐related vision problems are not missed.

What this paper adds

A minimum of three percent of primary school children had at least one cerebral visual impairment (CVI)‐related vision problem.

Fifteen percent of children with at least one CVI‐related vision problem had reduced visual acuity.

Seventy‐nine percent of children with CVI‐related vision problems were already receiving extra educational help.

Impact scores (indicating possible behavioural or developmental difficulties) from parents were more predictive than those from teachers.

Testing eye movements and fields with distraction increased the numbers of children classed as having impairments.
Young adults with type 1 diabetes and their experiences with diabetes follow‐up and participation in the DiaPROM pilot trial: A qualitative study
Authors: Hernar Ingvild , Graue Marit , Strandberg Ragnhild B. , Lie Silje S. , Sigurdardottir Arun K. , Richards David A. , Kolltveit Beate‐Christin H. , Haugstvedt Anne
Published: February 2021

Aim

To explore young adults' experiences of outpatient follow‐up appointments, completing electronic Patient‐Reported Outcome Measures (PROMs), and using the Problem Areas In Diabetes (PAID) scale during the Diabetes Patient‐Reported Outcome Measures (DiaPROM) pilot trial.

Methods

We performed a qualitative study among 19 young adults (aged 22–39 years) with type 1 diabetes who participated in the pilot trial. Between February and June 2019, we conducted individual, semi‐structured telephone interviews with participants from the intervention and control arms. We analysed the data using thematic analysis.

Results

Our analyses generated three themes, each with two subthemes: (1) Follow‐up with limitations; (i) Marginal dialogue about everyday challenges, (ii) Value of supportive relationships and continuity, indicate that previous follow‐up had been experienced as challenging and insufficient. (2) New insights and raised awareness; (i) More life‐oriented insights, (ii) Moving out of the comfort zone, suggest mostly positive experiences with completing questionnaires and discussing the PAID scores. (3) Addressing problem areas with an open mind; (i) Need for elaboration, (ii) Preparedness for dialogue, indicate that both openness and explanations were vital in the follow‐up.

Conclusions

Participants characterised the previous follow‐up as challenging and insufficient. They described completing and using the PAID as somewhat uncomfortable yet worthwhile. Our findings also suggest that by utilising diabetes distress data alongside health and biomedical outcomes, consultations became more attuned to the young adults' wishes and needs, mainly because the dialogue was more focused and direct. Hence, the PAID has the potential to facilitate person‐centredness and improve patient–provider relationships.
Characteristics of repeat non‐attenders at Diabetes Eye Screening Wales, a national community‐based diabetes‐related retinopathy screening service, during 2003‐2018
Authors: Thomas Rebecca L. , Cheung Wai‐Yee , Rafferty James M. , Luzio Stephen D. , Akbari Ashley , Owens David R.
Published: February 2021

Aims

To understand factors associated with repeat non‐attendance at screening for diabetes‐related retinopathy.

Methods

Retrospective observational study using anonymised data from Diabetic Eye Screening Wales for people with a full history of screening invitations and attendances was linked with primary and secondary care records held in the Secure Anonymised Information Linkage Databank. Repeat non‐attendance was defined as no record of attendance during any 36‐month period despite three cycles of annual screening invitations. The associations between repeat non‐attendance and potential risk factors were examined using multivariable logistic regression analysis, stratified according to type 1 and type 2 diabetes.

Results

A total of 18% with type 1 diabetes (1146/6513) and 8% with type 2 diabetes (12,475/156,525) were repeat non‐attenders. Participants attending their very first appointment were least likely to become repeat non‐attenders [odds ratio (95% confidence interval)]: type 1 diabetes: 0.12 (0.09, 0.17) and type 2 diabetes: 0.08 (0.07, 0.09). For both types of diabetes, those of a younger age, living in areas of higher deprivation and subject to multiple house moves were at greater risk of becoming repeat non‐attenders.

Conclusion/interpretation

A more tailored approach is needed for the younger population, those living in areas of higher deprivation and/or undergoing multiple residential relocation and to ensure attendance at their initial appointment to minimise future repeat non‐attendance.
Reducing the need for carbohydrate counting in type 1 diabetes using closed‐loop automated insulin delivery (artificial pancreas) and empagliflozin: A randomized, controlled, non‐inferiority, crossover pilot trial
Authors: Haidar Ahmad , Yale Jean‐Francois , Lovblom Leif Erik , Cardinez Nancy , Orszag Andrej , Falappa C. Marcelo , Gouchie‐Provencher Nikita , Tsoukas Michael A. , El Fathi Anas , Rene Jennifer , Eldelekli Devrim , Lanctôt Sebastien O. , Scarr Daniel , Perkins Bruce A.
Published: February 2021

Aim

To assess whether adding empagliflozin to closed‐loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control.

Materials and Methods

In an open‐label, crossover, non‐inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting) and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25 mg/day) or not, and crossed over to the comparator. Mean glucose for carbohydrate counting without empagliflozin (control) was compared with no meal announcement with empagliflozin (in the primary non‐inferiority comparison) and simple meal announcement with empagliflozin (in the conditional primary non‐inferiority comparison).

Results

Participants were aged 40 ± 15 years, had 27 ± 15 years diabetes duration and HbA1c of 7.6% ± 0.7% (59 ± 8 mmol/mol). The system with no meal announcement and empagliflozin was not non‐inferior (and thus reasonably considered inferior) to the control arm (mean glucose 10.0 ± 1.6 vs. 8.5 ± 1.5 mmol/L; non‐inferiority p = .94), while simple meal announcement and empagliflozin was non‐inferior (8.5 ± 1.4 mmol/L; non‐inferiority p = .003). Use of empagliflozin on the background of automated insulin delivery with carbohydrate counting was associated with lower mean glucose, corresponding to a 14% greater time in the target range. While no ketoacidosis was observed, mean fasting ketones levels were higher on empagliflozin (0.22 ± 0.18 vs. 0.13 ± 0.11 mmol/L; p < .001).

Conclusions

Empagliflozin added to automated insulin delivery has the potential to eliminate the need for carbohydrate counting and improves glycaemic control in conjunction with carbohydrate counting, but does not allow for the elimination of meal announcement.
Assessing the Powell policy review
Authors: Hetzel Robert
Published: February 2021

To understand both how it controls inflation and how it trades off inflation with its goal of maximum employment, the Federal Reserve System uses a Keynesian framework in which monetary policy moves the unemployment rate relative to a presumed full employment value, termed the NAIRU (non‐accelerating inflation rate of unemployment). Because it does not know the value of the NAIRU, it pursues an expansionary monetary policy until inflation rises. This policy risks reviving the inflationary monetary policy of the 1970s.
The fiscal and monetary response to COVID‐19: What the Great Depression has – and hasn't – taught us
Authors: Selgin George
Published: February 2021

Although some regard the New Deal of the 1930s as exemplifying an aggressive fiscal and monetary response to a severe economic crisis, the US fiscal and monetary policy responses to the COVID‐19 crisis have actually been far more substantial – and, so far, much more effective in reviving aggregate spending. Although many fear that these responses, and the large‐scale increase in bank reserves especially, must eventually cause unwanted inflation, the concurrent sharp decline in money's velocity has thus far more than offset any inflationary effects of money growth, while forward bond prices reflect a general belief that inflation will remain below 2 per cent for at least another decade. Notwithstanding the growth of the Fed's balance sheet, Fed authorities can always check inflation by sufficiently raising the interest return on bank reserves. Nonetheless, recent developments have heightened the risk of ‘fiscal dominance’ of monetary policy at some point in the future.
Debt, deficits, and inflation
Authors: Capie Forrest , Wood Geoffrey
Published: February 2021

This article sketches the theory of debt finance and cites historical evidence on the sustainability of debt. If it is accepted that the future should under the current circumstances of COVID‐19 help to alleviate the problems of the present, then debt finance is in principle appropriate. It need not lead to an explosive rise in the debt‐to‐GNP ratio. British history shows that the theory can work in practice. A satisfactory outcome, however, depends on government being reliable, honest, and competent. Trust is easily lost and hard to restore.
BMI and atrial fibrillation recurrence post catheter ablation: A dose‐response meta‐analysis
Authors: Pranata Raymond , Henrina Joshua , Yonas Emir , Putra Iwan C. S. , Cahyadi Irvan , Lim Michael A. , Munawar Dian A. , Munawar Muhammad
Published: February 2021

Introduction

The evidence on the association between obesity and atrial fibrillation (AF) recurrence was equivocal. We aimed to evaluate the dose‐response relationship between body mass index (BMI) and AF recurrence and adverse events.

Methods

A systematic literature search was conducted using PubMed, Europe PMC, EBSCO, ProQuest and Cochrane Library. Obesity was defined as BMI ≥28 kg/m2. The primary outcome was AF recurrence, and the secondary outcome was adverse events. Adverse events were defined as procedure‐related complications and cardio‐cerebrovascular events.

Results

There were a total of 52,771 patients from 20 studies. Obesity was associated with higher AF recurrence (Odds ratio [OR] 1.30 [95% confidence interval [CI] 1.16‐1.47],P < .001; I2: 72.7%) and similar rate of adverse events (OR 1.21 [95% CI 0.87‐1.67],P = .264; I2: 23.9%). Meta‐regression showed that the association varies by age (coefficient: −0.03,P = .024). Meta‐analysis of highest versus lowest BMI showed that the highest group had higher AF recurrence (OR 1.37 [95% CI 1.18‐1.58],P < .001; I2: 64.9%) and adverse events (OR 2.02 [95% CI 1.08‐3.76],P = .028; I2: 49.5%). The linear association analysis for AF recurrence was not significant (P = .544). The dose‐response relationship for BMI and AF recurrence was nonlinear (pnonlinearity < 0.001), the curve became steeper at 30‐35 kg/m2. For adverse events, an increase of 1% for every 1 kg/m2increase in BMI (OR 1.01 [95% CI 1.00‐1.02],P = .001), the relationship was nonlinear (pnonlinearity = 0.001).

Conclusion

Obesity was associated with higher AF recurrence in patients undergoing catheter ablation. High BMI might be associated with a higher risk for adverse events.

PROSPERO ID: CRD42020198787.