bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: hepatitis B—current and emerging therapies
Authors: Yardeni David , Ghany Marc G.
Published: February 2022

Background

The hepatitis B virus (HBV) affects an estimated 290 million individuals worldwide and is responsible for approximately 900 000 deaths annually, mostly from complications of cirrhosis and hepatocellular carcinoma. Although current treatment is effective at preventing complications of chronic hepatitis B, it is not curative, and often must be administered long term. There is a need for safe, effective, finite duration curative therapy.

Aim

Our aim was to provide a concise, up to date review of all currently available and emerging treatment options for chronic hepatitis B.

Methods

We conducted a search of PubMed, clinicaltrials.gov, major meeting abstracts and pharmaceutical websites for publications and communications on current and emerging therapies for HBV.

Results

Currently approved treatment options for chronic hepatitis B include peginterferon alpha‐2a and nucleos(t)ide analogues. Both options do not offer a ‘complete cure’ (clearance of covalently closed circular DNA (cccDNA) and integrated HBV DNA) and rarely achieve a ‘functional cure’ (hepatitis B surface antigen (HBsAg) loss). An improved understanding of the viral lifecycle, immunopathogenesis and recent advances in drug delivery technologies have led to many novel therapeutic approaches that are currently being evaluated in clinical trials including targeting of viral entry, cccDNA, viral transcription, core protein, and release of HBsAg and HBV polymerase. Additionally, novel immunological approaches that include targeting the innate and adaptive immune system and therapeutic vaccination are being pursued.

Conclusion

The breadth and scope of novel therapies in development hold promise for regimen/s that will achieve functional cure.
Model to predict on‐treatment restoration of functional HBV‐specific CD8+ cell response foresees off‐treatment HBV control in eAg‐negative chronic hepatitis B
Authors: Peña‐Asensio Julia , Calvo Henar , Miquel Joaquín , Sanz‐de‐Villalobos Eduardo , González‐Praetorius Alejandro , Torralba Miguel , Larrubia Juan‐Ramón
Published: February 2022

Background

Hepatitis B virus (HBV)‐specific CD8+ cell response restoration during nucleos(t)ide analogue (NUC) treatment could lead to off‐treatment HBV control in e‐antigen‐negative chronic hepatitis B (CHBe(−)).

Aim

To predict this response with variables involved in T‐cell exhaustion for use as a treatment stopping tool.

Methods

In NUC‐treated CHBe(−) patients, we considered a functional response in cases with HBV‐specific CD8+ cells against core and polymerase HBV epitopes able to proliferate and secrete type I cytokines after antigen encounter. We performed a logistic regression model (LRM) to predict the likelihood of developing this response, based on patient age (subrogate of infection length), HBsAg level, NUC therapy starting point and duration (antigenic pressure). We discontinued treatment and assessed HBV DNA dynamics, HBsAg decline and loss during off‐treatment follow‐up according to LRM likelihood.

Results

We developed an LRM that predicted the presence of a proliferative type I cytokine‐secreting CD8+ cell response, which correlated positively with treatment duration and negatively with treatment initiation after the age of 40 years and with age adjusted by HBsAg level. We observed a positive correlation between LRM probability and intensity of proliferation, number of epitopes with the functional proliferating response and type I cytokine secretion level. Off‐treatment, HBsAg loss, HBsAg decline >50% and HBV control were more frequent in the group with >90% LRM probability.

Conclusions

Short‐term low‐level antigen exposure and early long‐term NUC treatment influence the restoration of a functional HBV‐specific CD8+ cell response. Based on these predictors, a high likelihood of detecting this response at treatment withdrawal is associated with off‐treatment HBV control and HBsAg decline and loss.
Maxillary sinus floor augmentation comparing bovine versus porcine bone xenografts mixed with autogenous bone graft. A split‐mouth randomized controlled trial
Authors: Galindo‐Moreno Pablo , Abril‐García Dario , Carrillo‐Galvez Ana Belen , Zurita Federico , Martín‐Morales Natividad , O’Valle Francisco , Padial‐Molina Miguel
Published: February 2022

Aim

To compare the effectiveness of two xenografts for maxillary sinus floor augmentation in terms of clinical, radiographical, histologic, and molecular outcomes.

Materials and methods

A split‐mouth randomized clinical trial was conducted at the University of Granada. Ten consecutive patients in need of bilateral two‐staged maxillary sinus floor augmentation were included. Each patient received both biomaterials (porcine bone mineral and anorganic bovine bone), which were randomly assigned for bilateral sinus augmentation. The maxillary autogenous bone scraped from the sinus access window was mixed with each xenograft at a 20:80 ratio. After a healing period of 6 months, bone biopsies were collected with a trephine during the implant placement in the regenerated area. Histologic, histomorphometrical, immunohistochemical, and molecular outcomes were analyzed. Clinical and radiographical data throughout the treatment phases were also evaluated.

Results

The resulting anatomic features were similar between both groups. After six months of graft consolidation, the graft resorption rates were similar between both biomaterials. The histologic, histomorphometrical, and immunohistochemical results showed no statistical differences between groups.

Conclusion

Anorganic bovine bone and porcine bone mineral combined with maxillary autogenous cortical bone show similar biologic and radiologic features in terms of biomaterial resorption, osteoconduction, and osteogenesis when used for maxillary sinus floor augmentation.
High cutaneous amphiregulin expression predicts fatal acute graft‐versus‐host disease
Authors: Schultz Brittney , Miller Daniel D. , DeFor Todd , Blazar Bruce R. , Panoskaltsis‐Mortari Angela , Betts Brian C. , MacMillan Margaret L. , Weisdorf Daniel J. , Holtan Shernan G.
Published: February 2022

Background

Amphiregulin (AREG) is increased in circulation in acute graft‐versus‐host disease (aGVHD) and is associated with poor steroid response and lower survival. The expression of AREG in aGVHD target organs and its association with clinical outcomes are unknown.

Methods

We performed AREG immunohistochemical staining on skin specimens from 67 patients with aGVHD between the years 2010 and 2015. Two blinded reviewers assessed AREG expression and scored specimens with a semiquantitative scale ranging from 0 (absent) to 4 (most intense).

Results

Median AREG score of aGVHD cases was 3. Sixteen of 67 (23.9%) aGVHD cases had an AREG >3. High skin AREG expression (>3 vs. ≤3) was associated with increased overall clinical grade of aGVHD (52.9% vs. 33.4% clinical grade III‐IV, p = 0.02), reduced 3‐year overall survival (OS; 13% vs. 61%, p < 0.01), and increased 3‐year non‐relapse mortality (NRM; 56% vs. 20%, p = 0.05).

Conclusion

High skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor OS, and increased NRM.
Continous somatosensory evoked potentials and brain injury in neonatal hypoxic‐ischaemic encephalopathy treated with hypothermia
Authors: Lori Silvia , Bertini Giovanna , Bastianelli Maria Elena , Gabbanini Simonetta , Cossu Cesarina , Mortilla Marzia , Dani Carlo
Published: February 2022

Aim

To explore whether continuous somatosensory evoked potentials (SEPs) monitoring and video electroencephalograms (VEEG) accurately predict lesions observed on brain magnetic resonance imaging (MRI) in neonates with hypoxic‐ischaemic encephalopathy (HIE) receiving therapeutic hypothermia.

Method

This prospective study included 31 neonates (16 males, 15 females; mean [SD] gestational age 39 weeks [1.67]) who received therapeutic hypothermia for HIE. Therapeutic hypothermia was provided for 72 hours, with a target temperature of 33.0°C to 34.0°C and this was followed by a rewarming rate of approximately 0.5°C per hour, up to 36.5°C. SEPs and VEEG were evaluated simultaneously and continuously for 1 hour under normothermic conditions. MRI was carried out at a mean (SD) age of 6 (2) days.

Results

Our results showed a statistically significant correlation between continuous SEP and MRI scores (r=0.37, p=0.03), but not between the VEEG and MRI scores (r=0.30, p=0.09). Receiver operating characteristic analysis confirmed that continuous SEPs were highly specific and sensitive at predicting MRI abnormalities, whereas the VEEG had high specificity but low sensitivity.

Interpretation

Continuous monitoring of SEPs could provide early and important prognostic information in neonates with HIE.

What this paper adds

Early continuous somatosensory evoked potential (SEP) monitoring is correlated with hypoxic‐ischaemic encephalopathy (HIE) lesions.

Video electroencephalograms (VEEGs) are associated with lesions diagnosed after magnetic resonance imaging.

Both showed high specificity, but VEEGs did not show high sensitivity.

Continuously monitoring SEPs provides important information about HIE.
Association between preoperative diastolic dysfunction and early allograft dysfunction after orthotopic liver transplantation: An observational study
Authors: Vetrugno Luigi , Cherchi Vittorio , Zanini Victor , Cotrozzi Silvia , Ventin Marco , Terrosu Giovanni , Baccarani Umberto , Bove Tiziana
Published: February 2022

Objectives: To investigate the association between the grade of diastolic dysfunction (DD) and the occurrence of early allograft dysfunction (EAD) in liver transplant patients following the new 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines.

Methods: From January 2015 to December 2019, we retrospectively analyzed 83 patients who underwent orthotopic liver transplantation (OLTx) and their susceptibility to develop EAD according to the grade of preoperative DD. EAD was defined according to the criteria proposed by Olfhoff et al.; DD was defined with four parameters: E/A, e/e’, Left Atrium volume, and Tricuspid Regurgitation velocity.

Results: According to the ASE/EACVI guidelines grade II DD was detected in 20 patients (24.1%) undergoing OLTx. A statistically significant association was found between grade II DD and the occurrence of EAD (p‐value < 0.003). The Kaplan‐Meier analysis failed to find any significant difference between the survival probability, nevertheless at the end of a 90‐day follow‐up period, mortality showed a different trend in classes with more severe diastolic dysfunction.

Conclusion: According to the ASE/EACVI guidelines from 2016, patients with grade II DD seem to have a higher propensity to develop early allograft dysfunction EAD after OLTx. Our study advises a need for an urgent prospective multicenter study to elucidate the long‐term outcomes of liver transplants patients with diastolic dysfunction.
A comprehensive review of adverse events to drugs used in COVID‐19 patients: Recent clinical evidence
Authors: Ferreira‐da‐Silva Renato , Ribeiro‐Vaz Inês , Morato Manuela , Junqueira Polónia Jorge
Published: February 2022

Background

Since the breakthrough of the pandemic, several drugs have been used to treat COVID‐19 patients. This review aims to gather information on adverse events (AE) related to most drugs used in this context.

Methods

We performed a literature search to find articles that contained information about AE in COVID‐19 patients. We analysed and reviewed the most relevant studies in the Medline (via PubMed), Scopus and Web of Science. The most frequent AE identified were grouped in our qualitative analysis by System Organ Class (SOC), the highest level of the MedDRA medical terminology for each of the drugs studied.

Results

The most frequent SOCs among the included drugs are investigations (n = 7 drugs); skin and subcutaneous tissue disorders (n = 5 drugs); and nervous system disorders, infections and infestations, gastrointestinal disorders, hepatobiliary disorders, and metabolism and nutrition disorders (n = 4 drugs). Other SOCs also emerged, such as general disorders and administration site conditions, renal and urinary disorders, vascular disorders and cardiac disorders (n = 3 drugs). Less frequent SOC were eye disorders, respiratory, thoracic and mediastinal disorders, musculoskeletal and connective tissue disorders, and immune system disorders (n = 2 drugs). Psychiatric disorders, and injury, poisoning and procedural complications were also reported (n = 1 drug).

Conclusions

Some SOCs seem to be more frequent than others among the COVID‐19 drugs included, although neither of the studies included reported causality analysis. For that purpose, further clinical studies with robust methodologies, as randomised controlled trials, should be designed and performed.
Time dependence of hydraulic parameters estimation from transient analysis of mini disc infiltrometer measurements
Authors: Naik Aparimita Priyadarshini , Pekkat Sreeja
Published: February 2022

The transient analysis of mini disc infiltrometer (MDI) measurements is an established method for characterising near‐surface hydraulic characteristics of soils. The reliability of hydraulic characteristics obtained from transient analysis depends on the (1) adequacy of model, (2) adequacy of data, (3) measurement time and (4) measurement footprint. The measurement time dependence recommendations are reported only for a few soil textures, initially wet samples and tension infiltrometer (TI) with a higher measurement footprint than the MDI. This study investigated the adequacy of infiltration data (using cumulative linearization [CL] and differentiated linearization [DL]) and measurement time influence on the hydraulic parameters determined from the transient analysis of MDI measurements for six soil textures. The objective of the study is to identify suitable MDI measurement durations for different soil textures for the initially dry state, considering both adequacy of data and time fractionation (measurement time influence). The data adequacy time obtained from the DL (TDL) was found to be 0.8 times less than the value obtained from CL (TCL). The marginal difference in TDL and TCL had a significant influence on the determination of infiltration equation coefficient C1 and negligible influence on coefficient C2. The time fractionation procedure adopted for identifying adequate MDI measurement time (Tm) was found to be comparable based on sorptivity (S0) and hydraulic conductivity (K0). The average Tm was also comparable with TDL and TCL with a strong positive correlation. The C2 values obtained based on Tm, TDL, and TCL were in better agreement than the corresponding C1 values. The adequate MDI measurement times identified by considering Tm, TDL, and TCL were texture dependent, ranging from 45 min for silt to 120 min for silt loam and silty clay loam. For loamy sand, it was 50 min; for sand, it was 70 min, followed by 60 min for loam.
Is there a correlation between MOG‐associated disorder and SARS‐CoV‐2 infection?
Authors: Mariotto Sara , Carta Sara , Dinoto Alessandro , Lippi Giuseppe , Salvagno Gian Luca , Masin Laura , Alberti Daniela , Marignier Romain , Ferrari Sergio
Published: February 2022

Background and purpose

Anti‐myelin oligodendrocyte glycoprotein antibodies (MOG‐Abs) distinguish a group of inflammatory disorders which can be preceded by specific or non‐specific infections. A few single cases have been reported in association with SARS‐CoV‐2 infection, but a specific study on the correlation between COVID‐19 and myelin oligodendrocyte glycoprotein (MOG)‐associated disorder (MOGAD) has not yet been performed. The aim of this study was to determine the impact of the pandemic on this condition.

Methods

We analysed SARS‐CoV‐2 serology in patients newly diagnosed with MOGAD (1 August 2020 to 31 May 2021). MOG‐Ab‐seronegative age‐ and time‐matched subjects were used as controls. SARS‐CoV‐2 immunoglobulin G (IgG) levels were analysed using an anti‐SARS‐CoV‐2 US Food and Drug Administration‐approved ELISA assay and confirmed with a trimeric anti‐SARS‐CoV‐2 S1/S2 IgG immunochemiluminescent test, concomitantly assaying the anti‐receptor binding domain (RBD) of spike protein IgG and anti‐RBD total Ig. We actually compared the number of cases referred in each of the last 3 years.

Results

Presence of SARS‐CoV‐2 IgG antibodies was more common (12/30, 40%) in MOGAD patients than in controls (6/30, 20%), although the difference was not significant (p = 0.16; odds ratio 2.67, 95% confidence interval 0.85–9.17). The most common clinical presentations of MOGAD SARS‐CoV‐2‐seropositive patients included optic neuritis (n = 6) and myelitis (n = 3). The number of diagnosed cases increased over the last 3 years, in particular, when including cases referred to us before the COVID‐19 pandemic, in the initial phase of the first wave and in the late phase of the second wave (n = 9, rate 10.6% in 2019; n = 13, rate 12.3% in 2020; n = 15, rate 14.7% in 2021).

Conclusion

Our findings provide preliminary data on SARS‐CoV‐2 as a potential trigger of MOGAD.
Autotrophs are important contributors to benthic macroinvertebrate food webs in two tropical first‐order forest streams
Authors: Cortés‐Guzmán Daniela , Alcocer Javier , Planas Dolors
Published: February 2022

In tropical first‐order streams, the availability of basal resources changes according to tropical seasonality, i.e., dry and rainy seasons, with consequences for the food web structure. However, the seasonal variation in autotrophic and detrital pathways remains unclear. In this study, we aimed to establish whether the dominant pathway of the benthic macroinvertebrate food web in two tropical first‐order streams in the Lacandona rainforest, Mexico, relies on autotrophic or detrital food resources.

We evaluated the assimilation of autotrophic and detrital food resources through carbon and nitrogen stable isotope (δ13C and δ15N) analysis. We included the biomass of the macroinvertebrates sustained by the autotrophic and detrital pathways and the food web structure—trophic position, size structure, and degree of omnivory.

The biomass sustained by the detrital pathway remained similar throughout the year in both streams. In contrast, the biomass sustained by the autotrophic pathway was higher in the dry season than in the rainy season. The benthic macroinvertebrate food web had four levels, a poorly developed size structure, and an important degree of omnivory in both streams and in both seasons. It is likely that omnivory was a response to high resource variability and a strategy to reduce intraguild competition.

Autotrophs had a relatively higher importance than detritus since a much lower algae biomass sustained an equal or higher macroinvertebrate biomass, particularly in the dry season when the biomass of autotrophs increased. Seasonality influenced the macroinvertebrate food web by modifying the food resource availability and transference to higher trophic levels. However, the high frequency of omnivory reduced the seasonal changes in the food web structure.

Our results suggest that the autotrophic pathway plays an important role in maintaining the benthic macroinvertebrate food web in tropical streams. The relative importance of autotrophs in the macroinvertebrate food web is associated with seasonality, the rainfall pattern, and its effect on the stream hydrology.
Remote schooling during a pandemic: Visibly Muslim mothering and the entanglement of personal and political
Authors: Özdemir Şeyma
Published: February 2022

This experimental double‐conscious autoethnography narrates my navigation of remote learning after the COVID‐19 outbreak between mid‐March and early June 2020 as an apparent Muslim mother at a public school in upstate New York. To this end, using handwritten notes in a daily journal, I first delineated the process of becoming a visibly Muslim mother, which started earlier and reached a head after moving to the United States in 2018. In this way, using an autoethnographic style based on my experience of remote learning as a Muslim mother, I will present a dialog with feminist insights to reiterate that personal experience and cultural experience are incapable of being disentangled, that personal experience matters, and that all experience, however personal or private, is structured in a broader political and historical context.
Aerobic exercise in patients with haemophilia: A systematic review on safety, feasibility and health effects
Authors: Tomschi Fabian , Ransmann Pia , Hilberg Thomas
Published: February 2022

Background

Haemophilia is a congenital bleeding disorder going along with disease‐specific joint complications and general health implications attributed to the lack of daily movement. Recent guidelines recommend physical activity for people with haemophilia (PwH). Yet, aerobic exercise in PwH is little studied and seldomly prescribed by clinicans.

Aim

The aim of this systematic review is to investigate the safety, feasibility and health‐related efficiency of AE in PwH.

Methods

A systematic literature search according to the PRISMA guidelines was conducted (PubMed, Web of Science). Inclusion criteria were defined using PICOS. Methodological quality was assessed via TESTEX.

Results

Out of 789 studies identified, seven studies (three randomized controlled, two controlled, two single‐group prospective trails) were included. The TESTEX mean score was 8.1 (±3.8). AE was realized as aquatic exercise, nordic walking, treadmill running, bicycle riding and swimming. Neither bleeding rates nor the factor amount increased and AE led to diverse health‐related improvements.

Conclusions

Little research has been conducted evaluating AE in PwH. Yet, AE can be considered as safe and feasible when being supervised by experts. However, disease‐specific recommendations for AE are difficult to provide. Therefore, experts can currently only back AE recommendations on experience and nonhaemophilia‐specific general guidelines.
Comparative evaluation of complete and partial pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis: A randomized clinical trial
Authors: Ramani Ankita , Sangwan Pankaj , Tewari Sanjay , Duhan Jigyasa , Mittal Shweta , Kumar Vinay
Published: February 2022

Aim

The study aimed to compare the outcome of complete pulpotomy (CP) and partial pulpotomy (PP) techniques when utilised for the management of mature permanent teeth with carious pulpal exposure and symptomatic irreversible pulpitis (SIP).

Methodology

The study protocol was registered with ClinicalTrials.gov (NCT04397315). One hundred and six permanent mandibular molars with carious pulpal exposure and clinical diagnosis of SIP with periapical index ≤2, from patients aged between 18 and 40 years were randomly allocated in equal proportion to either CP or PP group. Allocated procedures were performed using standardised protocols. The allocated procedure was abandoned in cases where pulpal bleeding could not be controlled within 6 min using cotton pellets soaked in 3% sodium hypochlorite. MTA was used as a pulpotomy agent and teeth were restored using a base of glass ionomer followed by composite restoration. The pain was recorded by the patient preoperatively before administration of local anaesthesia and postoperatively every 24 h for 1 week using visual analogue scale. Success was analysed at 12 months based on clinical and radiographic examination. Mann–Whitney U test was used to compare age, pain scores and mean analgesic consumption between the groups. Categorical data were analysed using chi‐square test. Fisher's exact test was used to assess the clinical and radiographic success and incidence of pain. Kaplan–Meier analysis was used to assess the survival of teeth. A p‐value <.05 was considered as statistically significant.

Results

One hundred and one patients were analysed at follow up. Higher success was observed in CP (89.8%) in comparison to PP group (80.8%), but the difference was non‐significant statistically (p = .202). Although no significant difference was observed in pain incidence between the groups at 24 h (p = .496), a significant difference in pain intensities was observed between groups at all the tested time intervals, with lower values reported in CP group (p < .05).

Conclusions

Both CP and PP resulted in favourable outcomes in the management of cariously exposed permanent teeth with signs indicative of SIP. Given the more conservative nature of PP, it may be attempted first before proceeding to CP in such cases.
Angiogenesis in patient‐derived xenografts of odontogenic myxoma
Authors: Souza Juliana Cristina de , Bastos Victor Coutinho , Pereira Núbia Braga , Dias Adriana Abalen Martins , Avelar Gleide Fernandes de , Gomez Ricardo Santiago , Gomes Carolina Cavaliéri
Published: February 2022

Previously, by employing 3D organotypic tissue culture and patient‐derived xenograft (PDX) model, oral myxoma response to a MAPK/MEK inhibitor was observed. Gross examination of the tumour fragments obtained after 55 days of PDX grafting revealed increased capsule vascularization. Microscopic analyses showed blood capillaries intermixed with myxoma cells, but the origin of these capillaries, from mice or humans, was not established. This study aimed to investigate whether the endothelial cells observed in the myxoma PDX model are derived from the mouse or from the primary human tumour. Immunohistochemistry was performed on five tumour fragments from the PDX of myxoma after 55 days of implantation in mice. Immunopositivity for antibodies against human (HLA‐ABC) and mouse (H2 Db/H2‐D1) major histocompatibility complex class I (MHCI) was assessed in the endothelial cells. The endothelial cells in the PDX fragments revealed a membrane staining for the human MHCI protein in the PDX tumour and adjacent connective tissue capsule, indicating that capillaries were derived from the human tumour fragment. Considering the probable human origin of the endothelial cells from capillary blood vessels in the myxoma PDX, we conclude that this PDX model is an interesting model to study myxoma angiogenesis.
COVID‐19 and threats to irregular migrants in Kuwait and the Gulf
Authors: Shah Nasra M. , Alkazi Lubna
Published: February 2022

Prior to the COVID‐19 Pandemic, the Gulf region was home to ~29 million foreign residents, an estimated 20–40% of whom were residing there in an irregular status. Most of them had skilfully devised strategies to survive in this irregular situation, with friends and relatives acting as essential support networks. The COVID‐19 Pandemic suddenly disrupted this well‐established social order. This article outlines the lived experiences of 26 irregular migrants residing in Kuwait when the Pandemic occurred. Twelve of our interviewees were planning to leave in response to the amnesty declared on 1 April, while 14 were planning to stay or were uncertain. Network support continued to provide an essential element in enabling their survival. Intermediaries such as kafeels (sponsors) were often unavailable or unwilling to provide assistance. The health and welfare of irregular migrants require special policy attention since they now face an enhanced risk of being apprehended and deported.
Pressure ulcer prevalence and prevention interventions – A ten‐year nationwide survey in Sweden
Authors: Källman Ulrika , Hommel Ami , Borgstedt Risberg Madeleine , Gunningberg Lena , Sving Eva , Bååth Carina
Published: February 2022

The aim of this study was to describe pressure ulcer prevalence and prevention interventions in hospital care in Sweden based on nationwide surveys conducted over a 10‐year period. All Swedish hospitals were invited to participate in annual pressure ulcer prevalence surveys during the period 2011–2020. The data collection protocols included gender, age, skin assessment, risk assessment, and preventive interventions. In total, more than 130,000 patients were included in the ten prevalence surveys. The prevalence of pressure ulcers in Swedish hospital patients decreased significantly from 17.0 %to 11.4% between 2011 and 2020 and hospital‐acquired pressure ulcers decreased from 8.1% to 6.4% between 2018 and 2020. There was no significant decline in medicaldevice‐related pressure ulcers during the same period. The proportion of patients who were risk and skin assessed increased, as did the use of pressure‐reducing mattresses, sliding sheets, heel protection, and nrepositioning plans. This study shows that the implementation of a national patient safety program has had an impact on the nationwide prevalence of pressure ulcers in hospital care and the occurrence of prevention strategies. However, one in ten patients in Swedish hospitals still suffers from pressure ulcers. Further improvements can be made.
Ecology and diversity of culturable fungal species associated with soybean seedling diseases in the Midwestern United States
Authors: Pimentel Mirian F. , Srour Ali Y. , Warner Amanda J. , Bond Jason P. , Bradley Carl A. , Rupe John , Chilvers Martin I. , Rojas J. Alejandro , Jacobs Janette L. , Little Christopher R. , Robertson Alison E. , Giesler Loren J. , Malvick Dean , Wise Kiersten , Tenuta Albert , Fakhoury Ahmad M.
Published: February 2022

Aims

To isolate and characterize fungi associated with diseased soybean seedlings in Midwestern soybean production fields and to determine the influence of environmental and edaphic factors on their incidence.

Methods and Results

Seedlings were collected from fields with seedling disease history in 2012 and 2013 for fungal isolation. Environmental and edaphic data associated with each field was collected. 3036 fungal isolates were obtained and assigned to 76 species. The most abundant genera recovered were Fusarium (73%) and Trichoderma (11.2%). Other genera included Mortierella, Clonostachys, Rhizoctonia, Alternaria, Mucor, Phoma, Macrophomina and Phomopsis. Most recovered species are known soybean pathogens. However, non-pathogenic organisms were also isolated. Crop history, soil density, water source, precipitation and temperature were the main factors influencing the abundance of fungal species.

Conclusion

Key fungal species associated with soybean seedling diseases occurring in several US production regions were characterized. This work also identified major environment and edaphic factors affecting the abundance and occurrence of these species.

Significance and Impact of the Study

The identification and characterization of the main pathogens associated with seedling diseases across major soybean-producing areas could help manage those pathogens, and devise more effective and sustainable practices to reduce the damage they cause.
Outcome of cutaneous squamous cell carcinoma with microscopic residual disease after surgery and usefulness of postoperative radiotherapy: a retrospective cohort study
Authors: Revelles‐Peñas L. , Revilla‐Nebreda D. , Becerril S. , Corchete L.A. , Domínguez‐Rullán I. , Martins‐Lopes M. , Arias‐Rodríguez P. , Rodríguez‐Guitiérrez A. , Pérez‐Romansanta L.A. , Román‐Curto C. , Cañueto J.
Published: February 2022

Background

Microscopic residual disease (MRD) after surgery can be a challenging situation in cutaneous squamous cell carcinoma (CSCC) and there is a lack of evidence concerning its management.

Objective

To evaluate the prognosis of CSCC with MRD and the usefulness of postoperative radiotherapy (PORT) in CSCC with MRD.

Methods

Retrospective cohort study of CSCC with MRD through a 10‐year period (2010–2019) (n = 244). Disease‐free survival and event‐free survival were assessed using R (v.3.4.1), considering competing risks. Evaluated outcomes were local recurrence (LR), nodal metastases (NMs), and disease‐specific death (DSD).

Results

Median age was 88y (IQR: 10.5). A total of 145 (59.43%) were men and 69 (28.28%) were immunosuppressed. Median tumour diameter and thickness were 19 and 6.4 mm (IQR 11 and 5.5 mm). Patients treated by re‐excision had a relapse rate of 4.3% compared with 11.30% and 29.71% in those who received PORT and observation (P = 0.045). The use of PORT was associated with a lower risk of LR compared with observation (HR = 0.206 [0.049–0.859], P = 0.030), but not with a lower risk of NMs or DSDs. In the multivariable models, PORT was again associated with a lower risk of LR than observation (HR = 0.167 [0.039–0.708], P = 0.014), but not with lower risk of metastasis and death.

Conclusions

We always should try to obtain clear margins after surgery. PORT improves local control in CSCC with MRD, but when administered to the tumour bed, it does not reduce the risk of NM and DSD.
Drivers of racial/ethnic differences in perceived end‐of‐life care quality: More questions than answers
Authors: Bullock Karen , Makaroun Lena K.
Published: February 2022

This Editorial comments on the article by Kutney‐Lee et al. in this issue.
Effect of perceived stress, concern about hypoglycaemia and level of knowledge of management of the disease on glycaemic control in type 1 diabetes mellitus
Authors: Grau‐Del Valle Carmen , Marco‐Expósito José Francisco , Bosch‐Sierra Neus , Zaragoza‐Villena Begoña , Solá Eva , Montoya‐Castilla Inmaculada , Morillas Carlos , Bañuls Celia
Published: February 2022

Aims and objectives

To evaluate perceived stress, concern about hypoglycaemia and the level of knowledge of management of the disease in patients with type 1 diabetes mellitus and their relationship with glycaemic control, gender and age.

Background

Perceived stress and concern about hypoglycaemia are significant obstacles to achieving adequate glycaemic control in patients with type 1 diabetes mellitus, and notably influence management of the disease itself.

Material and Methods

A cross‐sectional study was carried out in 193 adult patients with type 1 diabetes mellitus. Study quality was scored using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies. Glycaemic control was evaluated by number and type of hypoglycaemic event and glycosylated haemoglobin. Questionnaires about hypoglycaemia concern (HFS II), perceived stress (PSS), unrecognised hypoglycaemia (Clarke Test) and level of knowledge of the disease were completed.

Results

Perceived stress was significantly associated with glycosylated haemoglobin (p < 0.001) and concern about hypoglycaemia (p < 0.037). With respect to level of knowledge, we observed that an advanced level was associated with lower glycosylated haemoglobin (p < 0.001), number (p < 0.001) and type (p < 0.001) of hypoglycaemic episode, and less perceived stress (p = 0.006). In addition, age was negatively correlated with perceived stress (p < 0.030) and positively correlated with the number of unrecognised hypoglycaemic episodes (p < 0.002), which was associated, in turn, with a higher number of daily glycaemia tests (p < 0.037) and concern about hypoglycaemia (p < 0.006).

Conclusion

In type 1 diabetes mellitus, perceived stress can negatively influence glycaemic control and concern about hypoglycaemia, and level of knowledge about the condition has a bearing on glycosylated haemoglobin levels, perceived stress and number and type of hypoglycaemic events. In addition, higher age is associated with more frequent unrecognised hypoglycaemic events. Relevance to clinical practice: It is essential to identify and address the psychological needs of patients with type 1 diabetes mellitus with the aim of achieving an adequate management of the disease itself and generating a change in future intervention strategies.
Corporate Leniency in a Dynamic World: The Preemptive Push of an Uncertain Future*
Authors: Gärtner Dennis L.
Published: February 2022

This paper investigates how leniency programs induce collusive offenders to self report in a dynamic setting, where the risk of independent detection evolves stochastically over time. We show how uncertainty about the future can push firms into preemptive application, and how these preemptive incentives can unravel to the point where firms apply long before the risk of detection is in any way imminent. For policy, the analysis suggests that a relatively harsh treatment of latecomers may be more important than offering high absolute reductions or even rewards, and that leniency should be available to firms who are already under investigation.
Analysis of differential metabolites of sunflower induced by virulent Verticillium dahlia V33 and hypovirulent Gibellulopsis nigrescens Vn‐1
Authors: Peng Jiao , Dong Bao‐Zhu , Wang Dong , Zhao Ying‐Jie , Meng Huan‐Wen , Zhou Hong‐You
Published: February 2022

Verticillium wilt is a widespread soil‐borne vascular disease of crops. Hypovirulent strains of pathogens show potential in providing cross‐protection against Verticillium wilt. To identify metabolites associated with the induction of resistance, gas chromatography–mass spectrometry‐based metabolomic technology was used to screen for differential metabolites induced by virulent (Verticillium dahlia V33) and hypovirulent (Gibellulopsis nigrescens Vn‐1) pathogen strains in sunflower (Helianthus annuus) roots. Forty‐eight differential metabolites were detected in the comparison between Vn‐1 and V33 inoculation treatments. Among these differential metabolites, the accumulation of 17 secondary metabolites was significantly higher in response to Vn‐1 inoculation compared with that after V33 inoculation. We selected nine differential metabolites for further analyses. Pyruvate, phenethylamine and 2‐phenylbutyric acid inhibited infection of Nicotiana benthamiana leaves by Botrytis cinerea and Phythophthora infestans. Pyruvate, phenethylamine and 2‐phenylbutyric acid induced H2O2 burst at 24 hours post‐spray (hps) treatment of N. benthamiana leaves with these organic acids. Quantitative RT‐PCR analysis revealed that pyruvate, phenethylamine and 2‐phenylbutyric acid significantly enhanced the expression of pathogenesis‐related genes at 24 hps, including PR1, NPR1 and PDF1.2. In addition, the activities of peroxidase, catalase, polyphenol oxidase and superoxide dismutase were increased. These results indicated that many metabolites were differentially induced by hypovirulent and virulent pathogen strains and were involved in resistance of sunflower against Verticillium wilt. Pyruvate, 2‐phenylbutyric acid and phenethylamine show potential for induction of plant resistance to pathogen infection.
Cultural Differences in Self‐Rated Health: The Role of Influence and Adjustment
Authors: Choi Jeong Ha , Miyamoto Yuri
Published: February 2022

Previous studies have demonstrated cross‐cultural differences in the levels of self‐rated health (SRH), an individual's overall perception of their health, and that Korea and Japan tend to show relatively poor SRH despite higher life expectancy compared to countries like the United States. While it has been suggested that response styles and macro‐level cultural values contribute to such differences, there is limited research on what other factors might be. The present study focused on influence and adjustment strategies as a potential cultural factor that could partly explain the cultural differences in SRH. Results from structural equation modeling have shown that Americans reported greater influence and positive reappraisal, plus a lower adjustment of goals than Japanese individuals, which partially explained the higher SRH among Americans than in the Japanese. These patterns were found even when a more objective measure of health (i.e., chronic conditions) was controlled for. Together, the findings highlight the role of influence and adjustment in understanding cultural differences in SRH.
Digital cognitive behaviour therapy for insomnia (dCBT‐I): Chronotype moderation on intervention outcomes
Authors: Faaland Patrick , Vedaa Øystein , Langsrud Knut , Sivertsen Børge , Lydersen Stian , Vestergaard Cecilie L. , Kjørstad Kaia , Vethe Daniel , Ritterband Lee M. , Harvey Allison G. , Stiles Tore C. , Scott Jan , Kallestad Håvard
Published: February 2022

Using data from 1721 participants in a community‐based randomized control trial of digital cognitive behavioural therapy for insomnia compared with patient education, we employed linear mixed modelling analyses to examine whether chronotype moderated the benefits of digital cognitive behavioural therapy for insomnia on self‐reported levels of insomnia severity, fatigue and psychological distress. Baseline self‐ratings on the reduced version of the Horne–Östberg Morningness–Eveningness Questionnaire were used to categorize the sample into three chronotypes: morning type (n = 345; 20%); intermediate type (n = 843; 49%); and evening type (n = 524; 30%). Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale were assessed pre‐ and post‐intervention (9 weeks). For individuals with self‐reported morning or intermediate chronotypes, digital cognitive behavioural therapy for insomnia was superior to patient education on all ratings (Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale) at follow‐up (p‐values ≤ 0.05). For individuals with self‐reported evening chronotype, digital cognitive behavioural therapy for insomnia was superior to patient education for Insomnia Severity Index and Chalder Fatigue Questionnaire, but not on the Hospital Anxiety and Depression Scale (p = 0.139). There were significant differences in the treatment effects between the three chronotypes on the Insomnia Severity Index (p = 0.023) estimated difference between evening and morning type of −1.70, 95% confidence interval: −2.96 to −0.45, p = 0.008, and estimated difference between evening and intermediate type −1.53, 95% confidence interval: −3.04 to −0.03, p = 0.046. There were no significant differences in the treatment effects between the three chronotypes on the Chalder Fatigue Questionnaire (p = 0.488) or the Hospital Anxiety and Depression Scale (p = 0.536). We conclude that self‐reported chronotype moderates the effects of digital cognitive behavioural therapy for insomnia on insomnia severity, but not on psychological distress or fatigue.
Hypothyroidism is prevalent among adult women with chronic lower urinary tract symptoms
Authors: Zargham Mahtab , Hajian Mohammad Reza , Alizadeh Farshid , Eslami Mohammad‐Javad , Khalili Boroujeni Noushin , Gholipour Farshad
Published: February 2022

Objective

To define the prevalence of hypothyroidism in women with chronic lower urinary tract symptoms (LUTS) and to compare the severity of each symptom between patients with hypothyroidism and controls.

Subjects and methods

In this prospective observational study, we screened all adult women who came to the urology clinic between March 2017 and September 2020, and enrolled patients with chronic LUTS in the study. We assessed thyroid function. We evaluated the severity of voiding and storage urinary symptoms by the International Prostate Symptom Score. We also assessed the severity of urge urinary incontinence (UUI) and stress urinary incontinence (SUI). For between‐group analysis, we selected age‐matched cases and controls and compared them regarding the distribution and severity of urinary symptoms.

Results

Seven hundred and twenty‐five women with a mean age of 51.7 ± 14.0 years were included in the final analysis. Two hundred fifty‐eight patients (35.6%) had hypothyroidism. Age‐matched case and control groups consisting of 210 patients each were selected. There was no significant difference in the severity and distribution of voiding LUTS and UUI between the study groups (P values >0.05). The severity of storage symptoms was lower in patients with hypothyroidism (P = 0.04). Sixty‐seven patients with hypothyroidism (31.9%) had SUI, which was significantly higher than controls (23.3%) (P = 0.03).

Conclusion

More than one‐third of women with chronic LUTS have hypothyroidism which is much more frequent than in the general population. We also suggest a possible relationship between hypothyroidism and the severity of SUI and an inverse relationship between hypothyroidism and storage symptoms.
Revisiting the embryogenesis of lip and palate development
Authors: Hammond Nigel L. , Dixon Michael J.
Published: February 2022

Clefts of the lip and palate (CLP), the major causes of congenital facial malformation globally, result from failure of fusion of the facial processes during embryogenesis. With a prevalence of 1 in 500–2500 live births, CLP causes major morbidity throughout life as a result of problems with facial appearance, feeding, speaking, obstructive apnoea, hearing and social adjustment and requires complex, multi‐disciplinary care at considerable cost to healthcare systems worldwide. Long‐term outcomes for affected individuals include increased mortality compared with their unaffected siblings. The frequent occurrence and major healthcare burden imposed by CLP highlight the importance of dissecting the molecular mechanisms driving facial development. Identification of the genetic mutations underlying syndromic forms of CLP, where CLP occurs in association with non‐cleft clinical features, allied to developmental studies using appropriate animal models is central to our understanding of the molecular events underlying development of the lip and palate and, ultimately, how these are disturbed in CLP.
The removal of tax expenditures from Spanish personal income tax: Impact on tax collection and income distribution
Authors: López‐Laborda Julio , Marín‐González Carmen , Onrubia Jorge
Published: February 2022

The paper estimates the consequences for tax revenue and income distribution of the removal of the tax expenditures from Spanish Personal Income Tax (IRPF) in place during the 2013 tax year. The paper concludes that the removal of all the tax expenditures analyzed would increase revenue by €24,457 million (37.9% of the IRPF actual collection), and that the redistributive effect, measured by the Reynolds‐Smolensky index, would be reduced by 1.1%. The paper also analyzes sundry hypothetical scenarios involving the refunding to individuals of the tax collected through the removal of tax expenditures, and its distributive impact is quantified.
Individual Differences and Skill Training in Cognitive Mapping: How and Why People Differ
Authors: Ishikawa Toru
Published: February 2022

Spatial ability plays important roles in academic learning and everyday activities. A type of spatial thinking that is of particular significance to people's daily lives is cognitive mapping, that is, the process of acquiring, representing, and using knowledge about spatial environments. However, the skill of cognitive mapping shows large individual differences, and the task of spatial orientation and navigation poses great difficulty for some people. In this article, I look at the motivation and findings in the research into spatial knowledge acquisition from an individual differences perspective. I also discuss major implications of the existence of large individual differences, particularly the possibility of improving cognitive mapping by training and adjusting navigation assistance to the wide variations in spatial aptitudes and preferences among people.