bluuebunny/crossref_metadata_2025 huggingface dataset:
Taurine supplementation increases survival of functional photoreceptors and decreases glial activation in RCS rats
Authors: Vacas Ana Martínez , Di Pierdomenico Johnny , Ortega Alejandro Gallego , Picaud Serge , Vidal‐Sanz Manuel , Perez Maria Paz Villegas , Garcia‐Ayuso Diego
Published: January 2022

Purpose

To analyse the neuroprotective effects of oral taurine administration in Royal College of Surgeons (RCS) rats.

Methods

Pigmented RCS rats (at postnatal day 21: P21) were administered taurine in drinking water (0.2 M) during 24 days. A group of untreated RCS rats were used as controls. Full field electroretinograms (ERG) in scotopic and photopic conditions, were performed at baseline (P21) and at the end of the study (P45). At this time, the retinas were cross‐sectioned, immunoreacted with antibodies against Iba1, GFAP and S and L/M opsins, and counterstained with DAPI. The number of nuclei rows in the outer nuclear layer (ONL) and of microglial cells in each retinal layer was quantified in 24 standard areas (8 per section in 3 sections per animal at 20x).

Results

Oral taurine supplementation significantly increased photoreceptor survival, decreased the number of microglial cells in all retinal layers and decreased GFAP immunoreactivity in macroglial cells. Cone and rod ERG responses were also significantly improved in taurine treated animals.

Conclusions

Oral taurine supplementation increases the survival of functional photoreceptors and decreases micro‐ and macroglial activation in RCS rats.
Diagnostic test accuracy of detection of diabetic macular signs using a hand‐held digital retinal camera at a non‐ophthalmic setting
Authors: Prabhath Piyasena Mapa , Yip Jennifer , Murthy Gudlavalleti V.S.
Published: January 2022

Purpose

The evidence on technical feasibility sceening for diabetic eye disease (DED) using hand‐held digital retinal cameras is scarce. We aimed to assess dignostic test accuracy (DTA) of screening for diabetic macular oedema (DMO) by trained physician graders in a non‐ophthalmic setting.

Methods

We trained 9 physicians on DED grading using digital imaging and best scored two graders selected for a validation study. 700 people with diabete mellitues (PwDM), and not previously screened or treated for DED were selected from a tertiary level medical clinic. 2‐feild (macular‐centred and disc‐centred) images were captured before and after pupil dilatation using a Visuscout‐100(R) hand‐held retinal camera and graded on‐site by the trained physician graders. The DTA of different levels of DED and DMO was assessed comparing physician’s grading with a retinologist’s clinical examination by mydriatic bio‐microscopy.

Results

Seven hundred eligible PwDM were screened and mean age was 60.8 years (SD ±10.08) and mean duration of DM was 9.9 years (SD ±8.09). Ungradable image proportion in non‐mydriatic imaging was 43.4% and decreased to 12.8% after mydrisis. Sensitivity of detection of any level of DMO was 81.0% (95% CI 73.3–88.7%) for grader‐1 (positive predictive value [PPV] 63.3%) and 75.3% (95% CI 66.8–83.7%) for grader‐2 (PPV 73.8%), using mydriatic imaging, after excluding ungradable images. The specificity was 96.0% (95% CI 94.9–97.1%) for grader‐1 (negative predictive value [NPV] 98.3%) and 97.8% (95% CI 96.9–98.6%) for grader‐2 (NPV 97.9%).

Conclusions

Sensitivity of DMO detection by physicians using images from a hand‐held retinal camera has limitations and would require further optimization before implementing in a programme. It shows the requirement of combining with 2ry level of referrable criteria, such as a visual acuity cut‐off, for achieving standard level of DTA.
Transcorneal electrical stimulation reduces the annual rate of visual field decline in retinitis pigmentosa
Authors: Stett Alfred , Schatz Andreas , Franklin Jeremy , Gekeler Florian
Published: January 2022

Purpose

In retinitis pigmentosa (RP) the visual field area (VFA) declines exponentially. We investigated whether the annual decline rate (ADR) can be slowed by transcorneal electrical stimulation (TcES).

Methods

We conducted an a posteriori analysis of data from 51 adult patients with RP who participated in an interventional, randomized, single‐masked study (clinicaltrials.gov: NCT01837901; Schatz et al., 2017, IOVS 58(1)). Patients were randomized into 3 groups stimulated with 0 mA (sham stimulation), 150% or 200% of their phosphene threshold, respectively. Over one year, TcES was applied monocularly, 30 min per week with biphasic current pulses (OkuStim, 5 ms each phase, 20 Hz, 0.2 to 1.0 mA). VFA were repeatedly assessed in both eyes (Octopus 900, target V4e). VFA values were normalized to percentage of baseline value, transformed into the natural logarithm, averaged within groups, and subjected to a weighted linear regression analysis. ADR was calculated from the slope of best fit line for both eyes in the sham group (n = 20) and in the treated group (n = 31, 150% and 200% groups pooled).

Results

In the sham group, for the stimulated eyes the ADR was 8.0% (F‐test for slope: p = 0.011) while for the non‐stimulated eyes it was 9.6% (p = 0.005). In the treated group, for the stimulated eyes the ADR was 3.4% (p = 0.276), and for the non‐stimulated eyes it was 7.0% (p = 0.035). The difference between the ADR in the stimulated and non‐stimulated eyes was evident when only eyes stimulated with >0.8 mA (n = 9) were included. The progression in the stimulated eyes had almost stopped, the ADR was 2.7% (p = 0.397) compared to 9.2% (p = 0.022) in the non‐stimulated eyes. The analysis is limited by data variability, sample size and observation period.

Conclusion

The analysis showed that the ADR can be markedly slowed by TcES in a dose‐dependent manner. Thus, regular use of TcES is an effective therapeutic method for slowing or arresting disease progression in RP.
A century of research on calcium silicate hydrate (C–S–H): Leaping from structural characterization to nanoengineering
Authors: Basquiroto de Souza Felipe , Sagoe‐Crentsil Kwesi , Duan Wenhui
Published: January 2022

Calcium silicate hydrate (C–S–H) gel is the glue of Portland cement that governs most of the physicochemical properties of concrete. Inherently, understanding and controlling its complex gel structure has long been an active area of research and deemed critical to realizing stronger, smarter, and more sustainable cementitious materials. Marking the 100th anniversary of Le Chatelier's publication on C–S–H colloids and crystalloids, here we present an overview of the broader developments in a century of research on C–S–H—covering the initial descriptions of its nanostructure, the onset of nanocharacterization, and molecular simulations to access its intricate texture and, ultimately, the design of nanoengineered ultra‐high‐performance C–S–H‐based materials. Overall, it is noted that further advances in characterization techniques and simulation methods remain pivotal to unraveling the nanoscale features of C–S–H and, thereby, drive the nanoengineering of cement materials at larger scales.
Hydrolysis protection and sintering of aluminum nitride powders with yttria nanofilms
Authors: O'Toole Rebecca J. , Hill Chanel , Buur Peter J. , Bartel Christopher J. , Gump Christopher J. , Musgrave Charles B. , Weimer Alan W.
Published: January 2022

Aluminum nitride (AlN) is a promising material for electronic substrates and heat sinks. However, AlN powders react with water that adversely affects final part properties and necessitates processing in organic solvents, increasing the cost of AlN parts. Small quantities of yttrium oxide (Y2O3) are commonly added to AlN particles to enable liquid phase sintering. To mitigate the reaction of AlN particles with water, particle atomic layer deposition (ALD) was used to coat AlN powders with conformal films of Y2O3 prior to densification and powder processing. When AlN particles were coated with 6 nm thick films of amorphous Y2O3, the hydrolysis reaction was significantly suppressed over 48 h, demonstrating that Y2O3 nanofilms on AlN powders act as a barrier coating in an aqueous solution. AlN powders with Y2O3 addition by particle ALD sintered to high relative densities (≥90% theoretical) after sintering at 1800°C for 50 min.
The emerging roles of exosomal long non‐coding RNAs in bladder cancer
Authors: Liu Qiang
Published: January 2022

Extracellular vesicles (EVs), especially exosomes, have been reported to play essential roles as extracellular messengers by transporting goods in various diseases, while their potential roles in bladder cancer (BC) still remain to be further studied. BC exhibits a high degree of chemoresistance and metastatic ability, which may be affected by cancer‐derived exosomes that carry proteins, lipids and RNA. To date, the most studied exosomal molecular cargo is long non‐coding RNA (lncRNA). Although there is increasing interest in its role and function, there is relatively little knowledge about it compared with other RNA transcripts. Nevertheless, in the past ten years, we have witnessed increasing interest in the role and function of lncRNA. For example, lncRNAs have been studied as potential biomarkers for the diagnosis of BC. They may play a role as a therapeutic target in precision medicine, but they may also be directly involved in the characteristics of tumour progression, such as metastasis, epithelial‐mesenchymal transition and drug resistance. Cancer cells are on chemotherapy acting. The function of lncRNA in various cancer exosomes has not yet been determined. In this review, we summarize the current studies about the prominent roles of exosomal lncRNAs in genome integrity, BC progression and carcinogenic features.
Single‐center, assessor‐blind study to evaluate the efficacy and safety of DA‐5520 topical gel in patients with acne scars: A pilot study
Authors: Han Hye Sung , Park Jae Wan , Shin Sun Hye , Yoo Kwang Ho , Sohn Young Sung , Kim Beom Joon
Published: January 2022

Background

Unlike various topical treatment options for acne vulgaris, options for acne scars mostly involve invasive interventions. So far, only a few clinical trials have investigated the effects of topical treatment for acne scars.

Objectives

We evaluated the safety and efficacy of DA‐5520, a recently developed topical gel for the treatment of different types of acne scars.

Methods

A 12‐week prospective, randomized, active‐controlled, evaluator‐blind, single‐center study involving 36 participants with acne scars was performed. Participants were randomized into four different groups at a 1:1:1:1 ratio: laser resurfacing with DA‐5520 application (test 1); laser resurfacing without DA‐5520 application (control 1); comedone extraction with DA‐5520 application (test 2); and comedone extraction without DA‐5520 application (control 2). For 12 weeks, participants in the two test groups applied DA‐5520 twice daily, while participants in the control groups applied moisturizers alone. Participants in the test 1 and control 1 groups received a single session of laser resurfacing at visit 1 (week 0). All participants were followed up at 1, 4, 8, and 12 weeks, and objective scar evaluation using the échelle d’évaluation clinique des cicatrices d'acné (ECCA) score was performed at each visit.

Results

Clinical improvement of acne scars, confirmed by the ECCA grading scale (1 for atrophic scar and 2 for hypertrophic scar), was observed after using DA‐5520 when combined with laser resurfacing or individually, and no associated adverse reactions were noted.

Conclusions

Preliminary results of this study revealed that DA‐5520 may be a promising new formulation for treating all type of acne scars.
Retrospective evaluation of patients with chronic spontaneous urticaria using omalizumab during the COVID‐19 pandemic
Authors: Koç Yıldırım Sema , Demirel Öğüt Neslihan , Erbağcı Ece
Published: January 2022

Introduction

Omalizumab (OMZ) is a monoclonal anti‐immunoglobulin E antibody used in patients with chronic spontaneous urticaria (CSU). The data about using OMZ during the coronavirus disease 19 (COVID‐19) pandemic are limited. The aim of this study was to evaluate the status of having COVID‐19 and relationships between COVID‐19, vaccination, and urticaria symptoms of CSU patients on OMZ.

Method

We conducted a retrospective cohort study of 36 adult CSU patients treated with OMZ. Demographic data, the results of COVID‐19 real‐time polymerase chain reaction (RT‐PCR), and vaccination status were recorded from the electronic medical records.

Results

Thirty‐six patients, 23 women, and 13 men were evaluated. The mean age was 45.81 years. Two patients were diagnosed with COVID‐19 while using OMZ. Four patients interrupted their OMZ treatment during the pandemic, and OMZ treatments were restarted in all patients. There were 28 patients who had at least one dose of vaccine (inactive and/or mRNA vaccine). Only one patient had an urticaria exacerbation after the first dose of mRNA vaccine.

Conclusion

As a result, our findings have shown that omalizumab treatment in CSU patients during the COVID‐19 pandemic does not increase the risk of COVID‐19 infection and omalizumab can be used safely.
Risk of venous and arterial thromboembolism in patients with giant cell arteritis and/or polymyalgia rheumatica: A Veterans Health Administration population‐based study in the United States
Authors: Michailidou Despina , Zhang Tianyu , Stamatis Pavlos , Ng Bernard
Published: January 2022

Background

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are systemic inflammatory diseases that primarily affect elderly women.

Objectives

To compare the risk of thromboembolic events and retinal vascular occlusions in GCA and/or PMR with that in osteoarthritis (OA), evaluating a veteran‐based population.

Methods

A total of 1535 patients with GCA, 10,265 with PMR, and 1203 with overlapping disease, as well as 39,009 age‐ and sex‐matched patients with OA were identified in this retrospective study. The incidence rate ratios (IRRs) of pulmonary embolism (PE), deep venous thrombosis (DVT), arterial thromboembolism, central retinal artery occlusion, and central retinal vein occlusion were calculated and examined over time. The cumulative incidence was plotted and hazard ratios (HRs) of thromboembolic events were calculated, adjusting for independent risk factors of thromboembolism.

Results

Patients with GCA and overlapping disease exhibited higher IRRs for all thromboembolic events compared to patients with OA. Patients with GCA had a higher risk of developing DVT and retinal vascular occlusions than those with overlapping disease (HR: 2.01, 95% confidence interval [CI]: 1.35–2.99, p < 0.001; HR: 2.37, 95% CI: 1.23–4.53, p = 0.009, respectively) or PMR alone (HR: 1.89, 95% CI: 1.50–2.41, p < 0.001; HR: 4.68, 95% CI: 3.10–7.07, p < 0.001, respectively). Patients with GCA had a higher risk of developing PE than those with PMR (HR: 1.55, 95% CI: 1.1–2.18, p = 0.01).

Conclusion

The risk of thromboembolic events differs between GCA, PMR, and overlapping diseases. Our findings may help predict the risk of thromboembolic events based on disease phenotype.
Salivary gland papillary adenocarcinoma with intestinal‐like features: Clinicopathologic, immunohistochemical, and genetic study of six cases
Authors: Liu Xiaoxiao , Zhang Ye , Zhou Chuan‐Xiang , Li Tie‐jun
Published: January 2022

Background

Salivary gland tumors with papillary architecture and intestinal‐like mucinous cytologic features are rare. Their clinicopathologic and genetic features are not fully understood, and whether they represent one separate entity remains unclear.

Methods

Six salivary adenocarcinomas with papillary architecture and intestinal‐like mucinous cytologic features were reported. Immunostaining was done for CK7, CK20, CDX2, SOX10, S100, MUC1, MUC2, and MUC5AC. Tumor DNA samples were extracted for Sanger sequencing. Previously reported morphology‐analogous cases were reviewed.

Results

Six cases involved the palate (2), retromolar region (1), submandibular region (1), tongue (1), and mandible (1). Five cases were followed up, with one case of recurrence 1 year after surgery, one death from cerebral infarction 7 days after surgery, and three cases without signs of recurrence or metastasis over 5 years. All cases had abundant mucinous production and presented a typical immunophenotype common to salivary primaries, CK7 & MUC1 positive, CK20 & CDX2 negative. Sanger sequencing demonstrated recurrent AKT1 E17K mutations in four cases (4/6, 66.7%). A review of reported salivary intestinal‐like tumors revealed 3 out of 13 cases presented with papillary morphology and CDX2 negative. Some salivary papillary neoplasms with mucinous cytologic features termed as intraductal papillary neoplasms or mucinous adenocarcinomas were also reported with AKT1 E17K mutations.

Conclusion

We describe 6 cases of salivary gland papillary adenocarcinoma with intestinal‐like mucinous cytologic features, which are different from conventional intestinal‐type adenocarcinoma, presenting a consistent immunophenotype of CK7 & MUC1 positive, CK20 & CDX2 negative and exhibiting recurrent AKT1 E17K mutations.
Fathers' infant‐directed speech and its effects on child language development
Authors: Ferjan Ramírez Naja
Published: January 2022

Infant‐directed speech (IDS), a speaking style distinguished by its higher pitch, slower tempo, and exaggerated intonation, has been documented in speech directed towards infants across many cultures and languages. Previous research shows that IDS in the context of parent‐infant interactions is associated with advances in children's language learning. While we have long known that fathers, like mothers, produce IDS, most research on IDS to this day has focussed exclusively on female (maternal) speech. In light of the recent societal changes which have increased fathers' time spent in hands‐on activities with children, I argue that the research on IDS needs to move away from using the maternal template. I first describe why IDS plays a central role in language development. I then outline known similarities and differences between paternal and maternal IDS, and point to potential biases and challenges within the research that has been conducted so far. Finally, I outline why investigators should strive to include fathers in research on IDS, and conclude with recommendations for follow‐up work that can help advance our understanding of fathers' contributions to children's linguistic development.
A food‐based approach could improve dietary adequacy for 12–23‐month‐old Eastern Ugandan children
Authors: Kimere Njeri C. , Nambooze Joweria , Lim Haeun , Bulungu Andrea L.S. , Wellard Kate , Ferguson Elaine. L.
Published: January 2022

Little is known about dietary adequacy, for young Ugandan children, or context‐specific food choices to improve it. This study estimated the percentage of breastfed 12–23‐month‐old rural Eastern Ugandan children (n = 114) at risk of inadequate intakes of 12 nutrients; and identified realistic food choices for improving it. In this cross‐sectional survey, dietary (weighed food records), anthropometric and socioeconomic data were collected. The percentages of children at risk of inadequate nutrient intakes were estimated, assuming 541 g/day of breast milk was consumed. The median nutrient densities of their complementary feeding diets were also compared with desired levels. Linear programming analyses were used to identify ‘problem nutrients’ (where requirements will be difficult to meet given dietary practices) and model food choices to improve dietary adequacy. Overall, 21.2% of children were stunted and 3.8% were wasted. A high percentage (>45%) of children were at risk of inadequate intakes, for nine of the 12 nutrients assessed, and dietary nutrient densities were below desired levels for seven of the 12 nutrients. Iron, calcium, thiamine and niacin were ‘problem nutrients’. Through careful selection of foods, modelling indicates that population level dietary adequacy can be achieved for eight of the 12 nutrients modelled. These choices include cows' milk, legumes, green leafy vegetables, sweet potatoes and fruits. Overall results suggest these high percentages of children at risk of inadequate nutrient intakes can be reduced through behaviour change interventions, although additional interventions may be required to ensure population‐level dietary adequacy for iron, thiamine and niacin.
The liberal/conservative nationalism divide: A distinction without a difference?
Authors: Daniel Rhianwen
Published: January 2022

Liberal nationalism has been the subject of increased attention in the wake of the 2010s rise in national populism. It has been seen to offer a concessionary form of national identity which is compatible with the liberal values of inclusivity and egalitarianism. This paper argues that recent attempts to delineate the contours of a specifically liberal national identity fail to highlight much that is distinctively liberal, as opposed to conservative, about its content. The criteria that such attempts propose typically apply almost equally to conservative accounts, thereby overshooting the target. However, further ideological excavation reveals that there is an alternative axis for distinguishing between liberal and conservative conceptions of national identity: democratic inclusivity. The paper further proposes that shifting the emphasis to this dimension, and to liberal and conservative accounts differing aims and formation processes, is conducive to both greater ideological transparency and bridging the gap between theory and practice.
A fungal microRNA‐like RNA subverts host immunity and facilitates pathogen infection by silencing two host receptor‐like kinase genes
Authors: Xu Ming , Li Guangyao , Guo Yan , Gao Yuqi , Zhu Lihua , Liu Zhaoyang , Tian Runze , Gao Chen , Han Pengliang , Wang Ning , Guo Feiran , Bao Jiyuan , Jia Conghui , Feng Hao , Huang Lili
Published: January 2022

Small RNAs (sRNAs) play important roles in various biological processes by silencing their corresponding target genes in most eukaryotes. However, cross‐kingdom regulation mediated by fungal microRNA‐like RNAs (milRNAs) in plant–pathogen interactions is still largely unknown.

Using molecular, genetic, histological, and biochemical approaches, we found that the apple tree Valsa canker pathogen Valsa mali milRNA Vm‐milR1 could suppress the host immunity by silencing two host receptor‐like kinase genes, MdRLKT1 and MdRLKT2.

Vm‐milR1 was highly induced during V. mali infection. Deletion of Vm‐milR1 precursor abolished the generation of Vm‐milR1 and reduced the virulence of V. mali. Inoculation of Vm‐milR1 deletion mutants induced the host defence responses, including reactive oxygen species (ROS) accumulation, callose deposition, and high expression of defence‐related genes. Furthermore, Vm‐milR1 was confirmed to be able to suppress the expression of MdRLKT1 and MdRLKT2 in a sequence‐specific manner. Moreover, overexpression of either MdRLKT1 or MdRLKT2 enhanced apple resistance to V. mali by activating the host defence responses. Furthermore, knockdown of MdRLKT1 or MdRLKT2 compromised the host resistance to V. mali.

Our study revealed that V. mali was equipped with Vm‐milR1 as an sRNA effector to silence host receptor‐like kinase genes, suppress the host defence responses, and facilitate pathogen infection.
Strategies to overcome the side effects of chimeric antigen receptor T cell therapy
Authors: Mirzaee Godarzee Mohadeseh , Mahmud Hussen Bashdar , Razmara Ehsan , Hakak‐Zargar Benyamin , Mohajerani Fatemeh , Dabiri Hamed , Fatih Rasul Mohammed , Ghazimoradi Mohammad Hossein , Babashah Sadegh , Sadeghizadeh Majid
Published: January 2022

Chimeric antigen receptor (CAR) therapy is a method directing T lymphocytes against antigens on the surface of tumors, increasing target cell elimination. Genetic engineering enhances the capability of immune cells to detect new antigens expressed on cell surfaces. CAR T cell therapy is a significant breakthrough for treating human malignancies; however, different side effects (e.g., cytokine release syndrome) restrict its application. Improving design and using various combined receptors enhance the performance of these cells. This review discusses limitations and risk factors associated with CAR T cell therapy. We also review some alternative approaches for developing the next generation of CAR T cells.
Oral leukoplakia: A clinicopathological study and malignant transformation
Authors: Tovaru Serban , Costache Mariana , Perlea Paula , Caramida Mariana , Totan Cosmin , Warnakulasuriya Saman , Parlatescu Ioanina
Published: January 2022

Objectives

To assess the clinicopathological characteristics of a cohort of patients with oral leukoplakia (OL) managed in a Romanian dental hospital and to evaluate the risk of malignant transformation (MT).

Materials and methods

We conducted a hospital‐based retrospective study using the clinical charts of patients diagnosed with OL that had complete clinical and histopathological evaluation followed up for 1–16 years.

Results

From 120 included patients, 68 (56.7%) were females, and 71 (59.2%) were current smokers. The homogeneous form was present in 60% of cases; the buccal mucosa was the most frequently involved site. MT was observed in 9 cases, which was more common in females and in those with dysplastic leukoplakia. A significant statistical association was found between MT and dysplasia grade (χ2 test: p = 0.007). MT occurred during a mean interval of time 75 months in both treated and non‐treated patients.

Conclusions

In this leukoplakia cohort, most of the lesions encountered were in smokers, clinically homogeneous and 62.5% proved histologically benign. But despite the clinically benign appearance of leukoplakia, tissue diagnosis of some cases was carcinoma. The results of the current study advocate the necessity for biopsy even in apparently homogeneous, clinically benign lesions. The malignization rate was 7.5%; two‐thirds were nonhomogeneous lesions.
Low‐intensity, long‐wavelength red light slows the progression of myopia in children: an Eastern China‐based cohort
Authors: Zhou Lei , Xing Chao , Qiang Wei , Hua Chaoqun , Tong Liyang
Published: January 2022

Purpose

To determine the effect of low‐intensity, long‐wavelength red light therapy (LLRT) on the inhibition of myopia progression in children.

Methods

A retrospective study was conducted. One hundred and five myopic children (spherical equivalent refractive error [SER] −3.09 ± 1.74 dioptres [D]; mean age, 9.19 ± 2.40 years) who underwent LLRT treatment (power 0.4 mW, wavelength 635 nm) twice per day for 3 min each session, with at least a 4‐h interval between sessions, and a control group of 56 myopic children (SER −3.04 ± 1.66 D; mean age, 8.62 ± 2.45 years) were evaluated. Both groups wore single‐vision distance spectacles. Each child returned for a follow‐up examination every 3 months after the initial measurements for a total of 9 months.

Results

At 9 months, the mean SER in the LLRT group was −2.87 ± 1.89 D, significantly greater than that of the control group (−3.57 ± 1.49 D,p < 0.001). Axial length (AL) changes were −0.06 ± 0.19 mm and 0.26 ± 0.15 mm in the LLRT group and control group (p < 0.001), respectively. The subfoveal choroidal thickness changed by 45.32 ± 30.88 μm for children treated with LLRT at the 9‐month examination (p < 0.001). Specifically, a substantial hyperopic shift (0.31 ± 0.24 D and 0.20 ± 0.14 D, respectively,p = 0.02) was found in the 8–14 year olds compared with 4–7 year old children. The decrease in AL in subjects with baseline AL >24 mm was −0.08 ± 0.19 mm, significantly greater than those with a baseline AL ≤24 mm (−0.04 ± 0.18 mm,p = 0.03).

Conclusions

Repetitive exposure to LLRT therapy was associated with slower myopia progression and reduced axial growth after short durations of treatment. These results require further validation in randomised controlled trials.
E‐commerce supply chains with considerations of cyber‐security: Should governments play a role?
Authors: Luo Suyuan , Choi Tsan‐Ming
Published: January 2022

E‐commerce supply chains and their members face risks from cyber‐attacks. Consumers who purchase goods online also risk having their private information stolen. Thus, businesses are investing to improve cyber‐security at a nontrivial cost. In this paper, we conduct a Stackelberg game‐theoretical analysis. In the basic model, we first derive the equilibrium pricing and cyber‐security level decisions in the e‐commerce supply chain. Based on real‐world practices, we then explore whether governments should impose cyber‐security penalty schemes. Our findings show that when the government is characterized by having sufficiently high emphasis on consumer surplus, implementing the penalty scheme is beneficial to social welfare. Then, we extend the analysis to examine how adopting systems security enhancing technologies (such as blockchain) will affect the government's choice of imposing penalty. We uncover that when it is beneficial to have government's penalty scheme, the technology benefit‐to‐cost ratio is a critical factor that governs whether the optimal penalty will be lower or higher with the adoption of systems security enhancing technologies. To generate more insights, we conduct further analyses for various extended modeling cases (e.g., with alliance, competition, and the defense‐level dependent penalty scheme) and find that our main results remain robust. One important insight we have uncovered in this study is that imposing government penalty schemes on cyber‐security issues may do more harm than good; while once it is beneficial to implement, the government should charge the heaviest possible fine. This finding may explain why in the real world, governments basically always adopt a polarized strategy, that is, either do not impose penalty or impose a super heavy penalty, on cyber‐security issues.
Improving the external validity of Antenatal Late Preterm Steroids trial findings
Authors: Hutcheon Jennifer A. , Liauw Jessica
Published: January 2022

Background

The external validity of randomised trials can be compromised when trial participants differ from real‐world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real‐world treatment benefits.

Objectives

To estimate the real‐world absolute risk reduction and number‐needed‐to‐treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real‐world populations.

Methods

Individual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population‐based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000–2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re‐estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population‐based (real‐world) sample.

Results

The real‐world absolute risk reduction was estimated to be −2.2 (95% CI −4.6, 0.0) cases of respiratory morbidity per 100, compared with −2.8 (95% CI −5.3, −0.3) in original trial data. Corresponding NNTs were 46 in the real‐world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of −3.7 vs. −1.2 per 100 respectively).

Conclusions

The absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real‐world situation.
Survey of SARS‐CoV‐2 in dogs and cats in high‐risk areas during the second wave of COVID‐19 outbreak, Thailand
Authors: Jairak Waleemas , Charoenkul Kamonpan , Chamsai Ekkapat , Udom Kitikhun , Chaiyawong Supassama , Hangsawek Aphinya , Waenkaew Suchart , Mungaomklang Anek , Tangwangvivat Ratanaporn , Amonsin Alongkorn
Published: January 2022

A cross‐sectional survey of SARS‐CoV‐2 in domestic dogs and cats was conducted in high‐risk areas, five subdistricts of Samut Sakhon Province, the epicenter of the second wave of the COVID‐19 outbreak in Thailand in February 2021. A total of 523 swab samples (nasal, oral, and rectal swabs) and 159 serum samples from dogs (n = 83) and cats (n = 93) were collected and tested for SARS‐CoV‐2 RNA and antibodies. All swab samples tested negative for SARS‐CoV‐2 RNA by real‐time RT‐PCR with three panels of specific primers and probes. Although all dogs and cats were negative for SARS‐CoV‐2 RNA, 3.14% (5/159) had anti‐N‐IgG antibodies against SARS‐CoV‐2 by indirect multispecies ELISA. Our results demonstrated SARS‐CoV‐2 exposure in domestic animals living in high‐risk areas during the second wave of the COVID‐19 outbreak in Thailand. Thus, the use of one health approach for monitoring SARS‐CoV‐2 in domestic animals in high‐risk areas of COVID‐19 outbreaks should be routinely conducted and will provide benefits to risk communications in communities.
The Effects of Supervised Exercise Training on Weight Control and Other Metabolic Outcomes in Patients With Type 2 Diabetes: A Meta-Analysis
Authors: Zhu Xingyun , Zhang Fang , Chen Jing , Zhao Yingxi , Ba Tianhao , Lin Chu , Lu Yingli , Yu Tao , Cai Xiaoling , Zhang Li , Ji Linong
Published: January 2022

Few studies have investigated the dose–response relationship between exercise and weight control. This study aimed to assess the effects of different types of supervised exercise training on weight control and other metabolic outcomes in patients with type 2 diabetes mellitus and explore the dose–response relationship between exercise volume/duration and these outcomes. PubMed/MEDLINE, Embase, and Cochrane databases were searched for studies between January 1980 and June 2019. Randomized control trials in type 2 diabetes mellitus patients with supervised exercise training versus control treatment were included. The primary outcome was changes in body weight (kg). The secondary outcomes included changes in waist circumference (cm) and total body fat percentage (%). Forty-two randomized control trials, including 3,625 patients with type 2 diabetes mellitus were included. Overall, exercise treatment was associated with significant reduction in body weight (weighted mean differences, −1.10 kg; 95% CI [−1.58, −0.62], p < .01), waist circumference (weighted mean differences, −2.51 cm; 95% CI [−3.25, −1.77], p < .01), and total body fat (weighted mean differences, −1.16%; 95% CI [−1.58%, −0.75%], p < .01). The percentage of total body fat was reduced by all types of exercise, with a significant difference between aerobic exercise and resistance exercise (p = .02) and a significant difference between combined exercise and resistance exercise (p < .01). A higher volume of aerobic exercise and a higher volume of resistance exercise were superior in reducing body weight. In conclusion, supervised exercise training improved metabolic outcomes in general, while different types and volume of exercises have their own merits.
Protection of Mice against Experimental Cryptococcosis by Synthesized Peptides Delivered in Glucan Particles
Authors: Specht Charles A. , Homan E. Jane , Lee Chrono K. , Mou Zhongming , Gomez Christina L. , Hester Maureen M. , Abraham Ambily , Rus Florentina , Ostroff Gary R. , Levitz Stuart M.
Published: January 2022

Cryptococcosis, due to infection by fungi of theCryptococcus neoformansspecies complex, is responsible for substantial morbidity and mortality in immunocompromised persons, particularly those with AIDS. Cryptococcal vaccines are a public health priority yet are not available for human use.
The Role of Integration Host Factor in Escherichia coli Persister Formation
Authors: Nicolau Samantha E. , Lewis Kim
Published: January 2022

Persisters are phenotypic variants that survive exposure to antibiotics through temporary dormancy. Mutants with increased levels of persisters have been identified in clinical isolates, and evidence suggests these cells contribute to chronic infections and antibiotic treatment failure.
Novel Viral Communities Potentially Assisting in Carbon, Nitrogen, and Sulfur Metabolism in the Upper Slope Sediments of Mariana Trench
Authors: Zhao Jiulong , Jing Hongmei , Wang Zengmeng , Wang Long , Jian Huahua , Zhang Rui , Xiao Xiang , Chen Feng , Jiao Nianzhi , Zhang Yongyu
Published: January 2022

The Mariana Trench harbors a substantial number of infective viral particles. However, very little is known about the identity, survival strategy, and potential functions of viruses in the trench sediments.
Clinical benefit of R-CHOP without splenectomy in stage I primary splenic diffuse large B-cell lymphoma
Authors: Rajendran Tara , Kini Jyoti Ramanath , Abna Aysha , Prasad Krishna
Published: January 2022

Primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is a relatively rare malignancy, and there are no optimal approaches for diagnosis and management. There are less invasive splenic biopsies that effectively obviate diagnostic and elective splenectomies. We report a man in his 50s with 2-day history of pain in the abdomen and who was found to have a splenic mass on PET-CT. A CT-guided core needle splenic biopsy confirmed the diagnosis of PS-DLBCL. He was managed with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alone, without splenectomy. The patient attained complete remission, and he is disease free at 6 years of follow-up.
Primary repair of multiligament knee injury with InternalBrace ligament augmentation
Authors: Paterson-Byrne Paul Andre , Wilson William Thomas , Hopper Graeme Philip , MacKay Gordon M
Published: January 2022

Multiligament injury of the knee usually occurs as a result of high-energy trauma causing tibiofemoral dislocation. These are rare but potentially limb-threatening injuries, frequently involving nerve or arterial damage and often leading to severe complex instability. Management generally favours surgical reconstruction of the affected ligaments, with controversy regarding optimal treatment. We present a severe multiligament knee injury (Schenk classification KD-IV involving both cruciate and both collateral ligaments) in a competitive showjumper. A combined arthroscopic/open technique of single-stage surgical repair and suture augmentation was used, repairing all affected ligaments. The patient made an excellent recovery, returning to work after 12 weeks and riding after 22 weeks. After 5-year follow-up, she has regained her previous level of competition without subsequent injury. Multiligament repair with suture augmentation is a viable approach to the management of knee dislocation injuries. We propose that this could provide superior outcomes to traditional reconstruction techniques using autograft or synthetic reconstruction.
Healthcare resource utilisation pattern and costs associated with herpes simplex virus diagnosis and management: a systematic review
Authors: Lee Shaun Wen Huey , Gottlieb Sami L , Chaiyakunapruk Nathorn
Published: January 2022

Objectives

Little is known about the economic burden of herpes simplex virus (HSV) across countries. This article aims to summarise existing evidence on estimates of costs and healthcare resource utilisation associated with genital and neonatal HSV infection.

Design

Systematic literature review.

Data sources

Seven databases were searched from inception to 31 August 2020. A focused search was performed to supplement the results.

Eligibility criteria

Studies which reported either healthcare resource utilisation or costs associated with HSV-related healthcare, including screening, diagnosis and treatment of genital HSV infection and neonatal herpes prevention and treatment.

Data extraction and synthesis

Two independent reviewers extracted data and assessed the risk of bias using the Larg and Moss’s checklist. All data were summarised narratively.

Results

Out of 11 443 articles, 38 were included. Most studies (35/38, 94.6%) were conducted in high-income countries, primarily the United States, and were more often related to the prevention or management of neonatal herpes (n=21) than HSV genital ulcer disease (n=17). Most analyses were conducted before 2010. There was substantial heterogeneity in the reporting of HSV-related healthcare resource utilisation, with 74%–93% individuals who sought care for HSV, 11.6%–68.4% individuals who received care, while neonates with herpes required a median of 6–34 hospitalisation days. The costs reported were similarly heterogeneous, with wide variation in methodology, assumptions and outcome measures between studies. Cost for screening ranged from US$7–100, treatment ranged from US$0.53–35 for an episodic therapy, US$240–2580 yearly for suppressive therapy, while hospitalisation for neonatal care ranged from US$5321–32 683.

Conclusions

A paucity of evidence exists on healthcare resource utilisation and costs associated with HSV infection, especially among low-income and middle-income countries. Future research is needed on costs and healthcare utilisation patterns to improve overall understanding of the global economic burden of HSV.
Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study
Authors: Ocskay Klementina , Juhász Márk Félix , Farkas Nelli , Zádori Noémi , Szakó Lajos , Szakács Zsolt , Szentesi Andrea , Erőss Bálint , Miklós Emőke , Zemplényi Antal , Birkás Béla , Csathó Árpád , Hartung István , Nagy Tamás , Czopf László , Izbéki Ferenc , Gajdán László , Papp Mária , Czakó László , Illés Dóra , Marino Marco V , Mirabella Antonello , Małecka-Panas Ewa , Zatorski Hubert , Susak Yaroslav , Opalchuk Kristina , Capurso Gabriele , Apadula Laura , Gheorghe Cristian , Saizu Ionut Adrian , Petersen Ole H , de-Madaria Enrique , Rosendahl Jonas , Párniczky Andrea , Hegyi Péter
Published: January 2022

Background/objectives

Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP.

Methods and analysis

The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort.

Ethics and dissemination

The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals.

Trial registration number

NCT04647097
Using machine learning to predict blood culture outcomes in the emergency department: a single-centre, retrospective, observational study
Authors: Boerman Anneroos W , Schinkel Michiel , Meijerink Lotta , van den Ende Eva S , Pladet Lara CA , Scholtemeijer Martijn G , Zeeuw Joost , van der Zaag Anuschka Y , Minderhoud Tanca C , Elbers Paul W G , Wiersinga W Joost , de Jonge Robert , Kramer Mark HH , Nanayakkara Prabath W B
Published: January 2022

Objectives

To develop predictive models for blood culture (BC) outcomes in an emergency department (ED) setting.

Design

Retrospective observational study.

Setting

ED of a large teaching hospital in the Netherlands between 1 September 2018 and 24 June 2020.

Participants

Adult patients from whom BCs were collected in the ED. Data of demographic information, vital signs, administered medications in the ED and laboratory and radiology results were extracted from the electronic health record, if available at the end of the ED visits.

Main outcome measures

The primary outcome was the performance of two models (logistic regression and gradient boosted trees) to predict bacteraemia in ED patients, defined as at least one true positive BC collected at the ED.

Results

In 4885 out of 51 399 ED visits (9.5%), BCs were collected. In 598/4885 (12.2%) visits, at least one of the BCs was true positive. Both a gradient boosted tree model and a logistic regression model showed good performance in predicting BC results with area under curve of the receiver operating characteristics of 0.77 (95% CI 0.73 to 0.82) and 0.78 (95% CI 0.73 to 0.82) in the test sets, respectively. In the gradient boosted tree model, the optimal threshold would predict 69% of BCs in the test set to be negative, with a negative predictive value of over 94%.

Conclusions

Both models can accurately identify patients with low risk of bacteraemia at the ED in this single-centre setting and may be useful to reduce unnecessary BCs and associated healthcare costs. Further studies are necessary for validation and to investigate the potential clinical benefits and possible risks after implementation.