bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings
Authors: Cheon Eun‐Jin , Bearden Carrie E. , Sun Daqiang , Ching Christopher R. K. , Andreassen Ole A. , Schmaal Lianne , Veltman Dick J. , Thomopoulos Sophia I. , Kochunov Peter , Jahanshad Neda , Thompson Paul M. , Turner Jessica A. , van Erp Theo G.M.
Published: February 2022

This review compares the main brain abnormalities in schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and 22q11.2 Deletion Syndrome (22q11DS) determined by ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium investigations. We obtained ranked effect sizes for subcortical volumes, regional cortical thickness, cortical surface area, and diffusion tensor imaging abnormalities, comparing each of these disorders relative to healthy controls. In addition, the studies report on significant associations between brain imaging metrics and disorder‐related factors such as symptom severity and treatments. Visual comparison of effect size profiles shows that effect sizes are generally in the same direction and scale in severity with the disorders (in the order SZ > BD > MDD). The effect sizes for 22q11DS, a rare genetic syndrome that increases the risk for psychiatric disorders, appear to be much larger than for either of the complex psychiatric disorders. This is consistent with the idea of generally larger effects on the brain of rare compared to common genetic variants. Cortical thickness and surface area effect sizes for 22q11DS with psychosis compared to 22q11DS without psychosis are more similar to those of SZ and BD than those of MDD; a pattern not observed for subcortical brain structures and fractional anisotropy effect sizes. The observed similarities in effect size profiles for cortical measures across the psychiatric disorders mimic those observed for shared genetic variance between these disorders reported based on family and genetic studies and are consistent with shared genetic risk for SZ and BD and structural brain phenotypes.
Paradoxical immune response in leishmaniasis: The role of toll‐like receptors in disease progression
Authors: Bamigbola Ifeoluwa E. , Ali Selman
Published: February 2022

Toll‐like receptors (TLRs), members of pattern recognition receptors, are expressed on many cells of the innate immune system, and their engagements with antigens regulate specific immune responses. TLRs signalling influences species‐specific immune responses during Leishmania infection; thus, TLRs play a decisive role towards elimination or exacerbation of Leishmania infection. To date, there is no single therapeutic or prophylactic approach that is fully effective against leishmaniasis. An in‐depth understanding of the mechanisms by which Leishmania species evade, or exploit host immune machinery could lead to the development of novel therapeutic approaches for the prevention and management of leishmaniasis. In this review, the role of TLRs in the induction of a paradoxical immune response in leishmaniasis was discussed. This review focuses on highlighting the novel interplay of TLR2‐ /TLR9‐driven resistance or susceptibility to 5 clinically important Leishmania species in human. The activation of TLR2/TLR9 can induce diverse anti‐Leishmania activities depending on the species of infecting Leishmania parasite. Infection with L. infantum and L. mexicana initiates TLR2/9 activation leading to host protective immune response, while infection with L. major, L. donovani and L. amazonensis trigger either a TLR2‐ /9‐related protective or non‐protective immune responses. These findings suggest that TLR2 and TLR9 are targets worth pursuing either for modulation or blockage to trigger host protective immune response towards leishmaniasis.
Supersonic jet noise from launch vehicles: 50 years since NASA SP-8072
Authors: Lubert Caroline P. , Gee Kent L. , Tsutsumi Seiji
Published: February 2022

In 1971, the U.S. National Aeronautics and Space Administration (NASA) published a seminal report—NASA SP-8072—which compiled the results of the early supersonic jet noise studies and provided methods to calculate the noise produced from launch vehicles. Fifty years later and despite known limitations, SP-8072 remains the foundation for much of the launch vehicle noise modeling today. This article reviews what has been learned about the physics of noise generation and radiation from free and impinging rocket plumes since the completion of SP-8072. State-of-the-art methods for the mitigation of launch vehicle noise are also reviewed. A discussion of launch vehicle noise modeling, from empirical to numerical and including reduced-order models of supersonic jets, points to promising approaches that can describe rocket noise characteristics not captured by SP-8072.
CCR7-guided neutrophil redirection to skin-draining lymph nodes regulates cutaneous inflammation and infection
Authors: Özcan A. , Collado-Diaz V. , Egholm C. , Tomura M. , Gunzer M. , Halin C. , Kolios A. G. A. , Boyman O.
Published: February 2022

Neutrophils are the first nonresident effector immune cells that migrate to a site of infection or inflammation; however, improper control of neutrophil responses can cause considerable tissue damage. Here, we found that neutrophil responses in inflamed or infected skin were regulated by CCR7-dependent migration and phagocytosis of neutrophils in draining lymph nodes (dLNs). In mouse models of Toll-like receptor–induced skin inflammation and cutaneous
Staphylococcus aureus
infection, neutrophils migrated from the skin to the dLNs via lymphatic vessels in a CCR7-mediated manner. In the dLNs, these neutrophils were phagocytosed by lymph node–resident type 1 and type 2 conventional dendritic cells. CCR7 up-regulation on neutrophils was a conserved mechanism across different tissues and was induced by a broad range of microbial stimuli. In the context of cutaneous immune responses, disruption of CCR7 interactions by selective CCR7 deficiency of neutrophils resulted in increased antistaphylococcal immunity and aggravated skin inflammation. Thus, neutrophil homing to and clearance in skin-dLNs affects cutaneous immunity versus pathology.
Epithelial Gasdermin D shapes the host-microbial interface by driving mucus layer formation
Authors: Zhang Jian , Yu Qianzhou , Jiang Danlu , Yu Kang , Yu Weiwei , Chi Zhexu , Chen Sheng , Li Mobai , Yang Dehang , Wang Zhen , Xu Ting , Guo Xingchen , Zhang Kailian , Fang Hui , Ye Qizhen , He Yong , Zhang Xue , Wang Di
Published: February 2022

Goblet cells and their main secretory product, mucus, play crucial roles in orchestrating the colonic host-microbe interactions that help maintain gut homeostasis. However, the precise intracellular machinery underlying this goblet cell–induced mucus secretion remains poorly understood. Gasdermin D (GSDMD) is a recently identified pore-forming effector protein that causes pyroptosis, a lytic proinflammatory type of cell death occurring during various pathophysiological conditions. Here, we reveal an unexpected function of GSDMD in goblet cell mucin secretion and mucus layer formation. Specific deletion of
Gsdmd
in intestinal epithelial cells (Δ
IEC
) led to abrogated mucus secretion with a concomitant loss of the mucus layer. This impaired colonic mucus layer in
Gsdmd

Δ
IEC

mice featured a disturbed host-microbial interface and inefficient clearance of enteric pathogens from the mucosal surface. Mechanistically, stimulation of goblet cells activates caspases to process GSDMD via reactive oxygen species production; in turn, this activated GSDMD drives mucin secretion through calcium ion–dependent scinderin-mediated cortical F-actin disassembly, which is a key step in granule exocytosis. This study links epithelial GSDMD to the secretory granule exocytotic pathway and highlights its physiological nonpyroptotic role in shaping mucosal homeostasis in the gut.
Children living with disabilities are neglected in severe malnutrition protocols: a guideline review
Authors: Engl Magdalena , Binns Paul , Trehan Indi , Lelijveld Natasha , Angood Chloe , McGrath Marie , Groce Nora , Kerac Marko
Published: February 2022

Purpose

Children living with disabilities are at high risk of malnutrition but have long been marginalised in malnutrition treatment programmes and research. The 2013 WHO guidelines for severe acute malnutrition (SAM) mention disability but do not contain specific details for treatment or support. This study assesses inclusion of children living with disabilities in national and international SAM guidelines.

Methods

National and international SAM guidelines available in English, French, Spanish or Portuguese were sourced online and via direct enquiries. Regional guidelines or protocols subspecialising in a certain patient group (eg, people living with HIV) were excluded. Eight scoping key informant interviews were conducted with experts involved in guideline development to help understand possible barriers to formalising malnutrition guidance for children living with disabilities.

Results

71 malnutrition guidelines were reviewed (63 national, 8 international). National guidelines obtained covered the greater part of countries with a high burden of malnutrition. 85% of guidelines (60/71) mention disability, although mostly briefly. Only 4% (3/71) had a specific section for children living with disabilities, while the remaining lacked guidance on consistently including them in programmes or practice. Only one guideline mentioned strategies to include children living with disabilities during a nutritional emergency. Most (99%,70/71) did not link to other disability-specific guidelines. Of the guidelines that included children living with disabilities, most only discussed disability in general terms despite the fact that different interventions are often needed for children with different conditions. Interviews pointed towards barriers related to medical complexity, resource constraints, epidemiology (eg, unrecognised burden), lack of evidence and difficulty of integration into existing guidelines.

Conclusion

Children living with disabilities are under-recognised in most SAM guidelines. Where they are recognised, recommendations are very limited. Better evidence is urgently needed to identify and manage children living with disabilities in malnutrition programmes. More inclusion in the 2022 update of the WHO malnutrition guidelines could support this vulnerable group.
Protocol for development of a core outcome set for clinical trials in melasma
Authors: Ibrahim Sarah A , Kang Bianca Y , Schlessinger Daniel I , Chiren Sarah G , Tang Jennifer C , Kirkham Jamie J , Schmitt Jochen , Poon Emily , Maher Ian A , Sobanko Joseph F , Cartee Todd V , Alam Murad
Published: February 2022

Introduction

Melasma is a pigmentation disorder of the skin. Characterised by brown to gray-brown patches on the face and neck, the condition predominantly affects women and has been associated with pregnancy, hormonal variation and sun exposure. Melasma can be disfiguring and anxiety-provoking, and quality of life is often adversely impacted. Management includes sun protection, laser and energy device therapy, topical and oral skin-bleaching agents and chemical peels. While clinical trials of melasma exist, there is a lack of consistency in reported outcomes, which has been a barrier to the aggregation of data in systematic reviews and meta-analyses. This protocol describes a planned process for development of a minimum set of outcomes (ie, ‘core outcome set’) that should be measured in all clinical trials of melasma.

Methods and analysis

An exhaustive list of potential outcomes will be extracted from four sources: (1) systematic literature review of outcomes in clinical trials; (2) semistructured patient interviews; (3) brochures, pamphlets, clinical trial registries, and other published and unpublished sources and documentation; and (4) interviews with non-patient, non-physician stakeholders, including federal regulators, industry scientists and non-physician providers. An international two-round Delphi process will then be performed to identify the outcomes deemed most important to patients and physicians. Subsequently, a consensus meeting will be convened to review and process the results, and to vote on a final set of core outcomes.

Ethics and dissemination

Ethics approval was provided by the Northwestern University Institutional Review Board (protocol ID: STU00201637). This study is registered with both the Core Outcome Measures in Effectiveness Trials and Cochrane Skin-Core Outcome Set Initiative initiatives, and this protocol is in accordance with the guidelines for protocol development of both groups. All findings from the study described in this protocol will be disseminated to all stakeholders involved in the development process and will be submitted for publication in peer-reviewed journals.

PROSPERO registration number

CRD42020214189.
Reporting of exercise dose and dosage and outcome measures for gaze stabilisation in the literature: a scoping review
Authors: Cole Keith R , Goodman Karen , Volland Lena
Published: February 2022

Objectives

The concept of this review is to examine and quantify the reporting of parameters of dose (duration, speed, head excursion) and dosage (daily and weekly frequency, duration) for gaze stabilisation exercises and to report on outcome measures used to assess change in gaze stabilisation following intervention. This review includes any population completing gaze stabilisation exercises.

Design

Scoping review.

Methods

We searched key terms in the following databases: PubMed, CINAHL, Scopus and Cochrane. Two researchers reviewed titles, abstracts and full-text articles for inclusion. Data retrieved included: patient diagnosis, specific interventions provided, dose and dosage of gaze stabilisation interventions and outcome measures.

Results

From the initial 1609 results, 138 studies were included. Data extraction revealed that only 13 studies (9.4%) reported all parameters of dose and dosage. Most studies used other interventions in addition to gaze stabilisation exercises. Half of the studies did not use a clinical or instrumented outcome measure of gaze stability, using only patient-reported outcome measures. Clinical tests of gaze stability were used in 21.1% of studies, and instrumented measures of gaze stability were used in 14.7% of studies.

Conclusions

Full reporting of the dose and dosage of gaze stabilisation interventions is infrequent, impairing the ability to translate current evidence into clinical care. Most studies did not use a clinical or instrumented measure of gaze stabilisation as outcome measures, questioning the validity of intervention effects. Improved reporting and use of outcome measures are necessary to establish optimal intervention parameters for those with gaze stability impairments.
Experiences and well-being of healthcare professionals working in the field of ultrasound in obstetrics and gynaecology as the SARS-CoV-2 pandemic were evolving: a cross-sectional survey study
Authors: Bourne Tom , Kyriacou Christopher , Shah Harsha , Ceusters Jolien , Preisler Jessica , Metzger Ulrike , Landolfo Chiara , Lees Christoph , Timmerman Dirk
Published: February 2022

Objective

Assess experience of healthcare professionals (HCPs) working with ultrasound in obstetrics and gynaecology during the evolving SARS-CoV-2 pandemic, given the new and unprecedented challenges involving viral exposure, personal protective equipment (PPE) and well-being.

Design

Prospective cross-sectional survey study.

Setting

Online international survey. Single-best, open box and Hospital Anxiety and Depression Scale (HADS) questions.

Participants

The survey was sent to 35 509 HCPs in 124 countries and was open from 7 to 21 May 2020. 2237/3237 (69.1%) HCPs from 115 countries who consented to participate completed the survey. 1058 (47.3%) completed the HADS.

Primary outcome measures

Overall prevalence of SARS-CoV-2, depression and anxiety among HCPs in relation to country and PPE availability.

Analyses

Univariate analyses were used to investigate associations without generating erroneous causal conclusions.

Results

Confirmed/suspected SARS-CoV-2 prevalence was 13.0%. PPE provision concerns were raised by 74.1% of participants; highest among trainees/resident physicians (83.9%) and among HCPs in Spain (89.7%). Most participants worked in self-perceived high-risk areas with SARS-CoV-2 (67.5%–87.0%), with proportionately more trainees interacting with suspected/confirmed infected patients (57.1% vs 24.2%–40.6%) and sonographers seeing more patients who did not wear a mask (33.3% vs 13.9%–7.9%). The most frequent PPE combination used was gloves and a surgical mask (22.3%). UK and US respondents reported spending less time self-isolating (8.8 days) and lower satisfaction with their national pandemic response (37.0%–43.0%). 19.8% and 8.8% of respondents met the criteria for moderate to severe anxiety and depression, respectively.

Conclusions

Reported prevalence of SARS-CoV-2 in HCPs is consistent with literature findings. Most respondents used gloves and a surgical mask, with a greater SARS-CoV-2 prevalence compared with those using ‘full’ PPE. HCPs with the least agency (trainees and sonographers) were not only more likely to see high-risk patients but also less likely to be protected. A fifth of respondents reported moderate to severe anxiety.
Supporting community health workers in fragile settings from a gender perspective: a qualitative study
Authors: Raven Joanna , Wurie Haja , Baba Amuda , Bah Abdulai Jawo , Dean Laura , Hawkins Kate , Idriss Ayesha , Kollie Karsor , Nallo Gartee E , Steege Rosie , Theobald Sally
Published: February 2022

Objective

To explore how gender influences the way community health workers (CHWs) are managed and supported and the effects on their work experiences.

Setting

Two districts in three fragile countries. Sierra Leone—Kenema and Bonthe districts; Liberia—two districts in Grand Bassa county one with international support for CHW activities and one without: Democratic Republic of Congo (DRC)—Aru and Bunia districts in Ituri Province.

Participants and methods

Qualitative interviews with decision-makers and managers working in community health programmes and managing CHWs (n=36); life history interviews and photovoice with CHWs (n=15, in Sierra Leone only).

Results

While policies were put in place in Sierra Leone and Liberia to attract women to the newly paid position of CHW after the Ebola outbreak, these good intentions evaporated in practice. Gender norms at the community level, literacy levels and patriarchal expectations surrounding paid work meant that fewer women than imagined took up the role. Only in DRC, there were more women than men working as CHWs. Gender roles, norms and expectations in all contexts also affected retention and progression as well as safety, security and travel (over long distance and at night). Women CHWs also juggle between household and childcare responsibilities. Despite this, they were more likely to retain their position while men were more likely to leave and seek better paid employment. CHWs demonstrated agency in negotiating and challenging gender norms within their work and interactions supporting families.

Conclusions

Gender roles and relations shape CHW experiences across multiple levels of the health system. Health systems need to develop gender transformative human resource management strategies to address gender inequities and restrictive gender norms for this critical interface cadre.
Improving the quality of the performance and delivery of continuous renal replacement therapy (CRRT) to critically ill patients across a healthcare system: QUALITY CRRT: a study protocol
Authors: Opgenorth Dawn , Reil Ellen , Lau Vincent , Fraser Nancy , Zuege Danny , Wang Xiaoming , Bagshaw Sean M , Rewa Oleksa
Published: February 2022

Introduction

Continuous renal replacement therapy (CRRT) is a continuous form of dialysis used to support critically ill patients with acute kidney injury. The ideal delivery of CRRT requires ongoing monitoring and reporting to adjust practice and deliver optimal therapy. However, this practice occurs variably.

Methods

QUALITY CRRT is a multicentre, prospective, stepped-wedged, interrupted time series (ITS) evaluation of the effectiveness, safety and cost of implementing a multifaceted CRRT quality assurance and improvement programme across an entire healthcare system. This study will focus on the standardisation of CRRT programmes with similar structure, process and outcome metrics by the reporting of CRRT key performance indicators (KPIs). The primary outcome will be the quarterly performance of CRRT KPIs. Secondary outcomes will include patient-centred outcomes and economic outcomes. Analysis will compare pre-implementation and post-implementation groups as well as for the performance of KPIs using an ITS methodology. The health economic evaluation will include a within-study analysis and a longer-term model-based analysis.

Discussion

The effective delivery of CRRT to critically ill patients ideally requires a standardised approach of best practice assessment and ongoing audit and feedback of standardised performance measures. QUALITY CRRT will test the application of this strategy stakeholder engagement and stepped-wedged implementation across an entire healthcare system.

Ethics and dissemination

This study has received ethics approval. We will plan to publish the results in a peer-reviewed journal.

Trial registration number

NCT04221932.

Protocol version

1.0 (15 June 2020).
GPs’ views on the implementation of combined lifestyle interventions in primary care in the Netherlands: a qualitative study
Authors: van der Heiden W , Lacroix JPW , Moll van Charante EP , Beune EJAJ
Published: February 2022

Objectives

Prevention and lifestyle support are emerging topics in general practice. Healthcare insurance companies reimburse combined lifestyle interventions (CLIs) in the Netherlands since January 2019. CLIs support people with overweight (body mass index, BMI 25–30) or obesity (BMI >30) to reduce weight in peer groups. General practitioners (GPs) are key in the successful implementation of lifestyle interventions in primary care. This study explored GPs’ experiences and views on the implementation of CLIs to identify barriers and facilitators to the successful implementation in primary care.

Design

Qualitative study using semistructured interviews. Content analysis consisted of thematic coding and mapping a first stage of predefined and second stage of iterative evolving set of themes.

Setting

GPs were interviewed in a variety of primary care practices between February and April 2019.

Participants

Fifteen GPs were purposively recruited for semi-structured interviews through snowballing.

Results

Experiences with lifestyle support among GPs ranged from referring patients to other healthcare professionals to taking a proactive role in lifestyle support themselves. Whether or not GPs took an active role in lifestyle support was related to their belief in the effect of lifestyle interventions. Overall, GPs had little experience with CLI in every day practice. Perceived barriers were a lack of availability of CLIs in the region and the potential lack of added value of CLIs on top of existing lifestyle support. Perceived facilitators were coordination of care provision by GP cooperatives and monitoring of the CLI implementation and their results. Reimbursement of CLIs without any costs for participants enabled application.

Conclusion

The importance of lifestyle interventions in primary care was acknowledged by all GPs, but they differed in their level of experience with providing lifestyle support and awareness of CLIs. Successful integration of CLIs with primary care requires a solid promotion, a well-coordinated implementation strategy and structural evaluation of long-term effectiveness.
Vitreoretinal specialists compared with residents on outcomes of primary laser retinopexy in preventing retinal detachment in 958 eyes
Authors: Moussa George , Samia-Aly Emma , Ch'ng Soon , Lett Kim Son , Mitra Arijit , Tyagi Ajai K , Sharma Ash , Andreatta Walter
Published: February 2022

Objective

Retinal tears are the most common vitreoretinal (VR) emergency and retinopexy aims to reduce the risk of rhegmatogenous retinal detachment (RRD). Currently retinal laser is a required competence by the Royal College of Ophthalmologists for residents. We report 6-month detachment rate and repeat retinopexy rate of VR specialists compared with residents.

Methods and analysis

A retrospective, consecutive study of 958 eyes undergoing primary laser retinopexy (slit lamp or indirect laser) from January 2017–2020 was divided into training level by operator: specialty training (ST) 2–3, ST4–5, ST6–7 and VR specialists.

Results

We report an overall 6-month RRD rate in 32/958 (3.3%) (ST2–3: 9/221 (4.1%), ST4–5: 15/373 (4.0%), ST6–7: 2/72 (2.8%) and VR specialists: 6/292 (2.1%)). We additionally report a repeat retinopexy rate of 189/958 (19.7%), (ST2–3: 44/221 (19.9%), ST4–5: 80/373 (21.4%), ST6–7: 16/72 (22.8%) and VR specialists: 49/292 (16.8%)]). Multivariable Cox survival regression analysis showed significant risk factors for developing RRD include male gender (p=0.018), high myopia (≤−6.00 Dioptres, p=0.004), ST2–3 (p=0.022) and ST4–5 (p=0.040) (relative to VR specialists) and by ST6–7, no significance was found (p=0.151). Significantly higher repeat retinopexy rates were associated with horseshoe tears (relative to round holes, p<0.001) and high myopia (p=0.026) with no difference between different training levels.

Conclusion

There was a decreasing trend in RRD rate following primary retinopexy with increase in training. Although junior residents had a higher RRD rate than VR specialists, it was still favourable relative to other large case series. While there was no difference in subsequent laser retinopexy rate between training levels, the retreatment rate was associated with the type of tear and high myopia.
Deep learning-based classification of retinal vascular diseases using ultra-widefield colour fundus photographs
Authors: Abitbol Elie , Miere Alexandra , Excoffier Jean-Baptiste , Mehanna Carl-Joe , Amoroso Francesca , Kerr Samuel , Ortala Matthieu , Souied Eric H
Published: February 2022

Objective

To assess the ability of a deep learning model to distinguish between diabetic retinopathy (DR), sickle cell retinopathy (SCR), retinal vein occlusions (RVOs) and healthy eyes using ultra-widefield colour fundus photography (UWF-CFP).

Methods and Analysis

In this retrospective study, UWF-CFP images of patients with retinal vascular disease (DR, RVO, and SCR) and healthy controls were included. The images were used to train a multilayer deep convolutional neural network to differentiate on UWF-CFP between different vascular diseases and healthy controls. A total of 224 UWF-CFP images were included, of which 169 images were of retinal vascular diseases and 55 were healthy controls. A cross-validation technique was used to ensure that every image from the dataset was tested once. Established augmentation techniques were applied to enhance performances, along with an Adam optimiser for training. The visualisation method was integrated gradient visualisation.

Results

The best performance of the model was obtained using 10 epochs, with an overall accuracy of 88.4%. For DR, the area under the receiver operating characteristics (ROC) curve (AUC) was 90.5% and the accuracy was 85.2%. For RVO, the AUC was 91.2% and the accuracy 88.4%. For SCR, the AUC was 96.7% and the accuracy 93.8%. For healthy controls, the ROC was 88.5% with an accuracy that reached 86.2%.

Conclusion

Deep learning algorithms can classify several retinal vascular diseases on UWF-CPF with good accuracy. This technology may be a useful tool for telemedicine and areas with a shortage of ophthalmic care.
Bleeding management in palliative medicine: subcutaneous tranexamic acid - retrospective chart review
Authors: Howard Paul , Curtin John
Published: February 2022

Objectives

To investigate the efficacy and safety of subcutaneously (SC) administered tranexamic acid.

Methods

A retrospective chart review of the use of SC tranexamic acid in a single palliative care centre. We reviewed the use of this approach since it was introduced in our locality 2 years ago. All clinical notes, medication administration records and infusion monitoring documentation were examined to ascertain therapeutic aim, efficacy and tolerability.

Results

SC tranexamic acid was administered to 22 patients. The most common causes of bleeding were coagulopathy (5), bleeding tumours (9) and thrombocytopaenia (5). The therapeutic aim was either to prevent (6) or treat (16) bleeding and was achieved in 17/22 patients. During this 2-year period, our experience evolved resulting in a greater use of short bolus infusions to achieve more rapid control of bleeding events. Both short and continuous SC infusions were well tolerated with no instances of SC site reactions. One patient developed a suspected arterial thrombus in the last hours of life around the time of converting from oral (PO) to SC tranexamic acid.

Conclusions

SC administration of tranexamic acid appears to be an effective and well tolerated alternative option for the palliative management of bleeding when the PO and intravenous routes are not available. Further research is needed to clarify tranexamic acid’s safety in palliative populations.
The phylogenetic affinity of the Ordovician trilobitesAgerina,Forteyaspisgen. nov., and related genera, with new and revised species from Canada and the United States
Authors: Karim Talia S. , Adrain Jonathan M.
Published: February 2022

A phylogenetically related group of variably well-known Ordovician trilobites have in the past been assigned to six separate genera and a number of families, and their taxonomic cohesiveness has not always been recognized. When most of them have been understood to form an evolutionarily related group, they have historically most often been assigned to the genus Agerina Tjernvik, 1956, and assigned initially to Bathyuridae Walcott, 1886, and more recently to Leiostegiidae Bradley, 1925. The systematics of this group is revised, and its 25 formally named species are assigned to four potentially monophyletic genera. Ontogenetic information from a new silicified species, together with some adult morphology, demonstrates that the group is unambiguously related to the Ordovician family Phillipsinellidae Whittington, 1950, to which it is assigned as a suite of less derived genera. The new genus Forteyaspis (type species Forteyaspis idoli sp. nov. from the Darriwilian of western Newfoundland, Canada) is proposed for four Laurentian species, and other species are assigned to the genera Agerina, Brackebuschia Harrington and Leanza, 1957, and Hexianella Zhang in Qiu et al. Other new species are Agerina boygeorgei (Floian, Nevada, USA) and Forteyaspis adamanti (Floian, western Newfoundland, Canada). Forteyaspis norrisi (Ludvigsen, 1980) is photographically revised.
Modeling the effect of the inclination angle on the dynamic response of a biaxially pre-stressed plate
Authors: Daşdemir Ahmet
Published: February 2022

In this study, I report on an investigation of the forced vibrations procured by an arbitrary angled time-harmonic loading from a plate based on a rigid foundation. The study was formulated according to the three-dimensional linearized theory of elasticity for solids under initial stress (TLTESIS). It was assumed throughout the investigation that there is a rigid clamped state between the system and the rigid ground; further, it was assumed that the plate was exposed to biaxially static initial stresses. Given this, a mathematical model was developed, and then solved using a three-dimensional finite element method (3D-FEM). Presented are numerical investigations that illustrate the influence of changes in the inclination of the force, as well as other important factors such as dimensionless frequency parameters, on the dynamic behavior of the system. In particular, the results indicate that the effect the initial stresses have on the dynamic stress distribution character increases with the aspect ratio but decreases with the thickness ratio.
Resonance contributions in $$B^-\rightarrow K^+K^-\pi ^-$$ within the light-cone sum rule approach
Authors: Shi Yu-Ji , Meißner Ulf-G. , Zhao Zhen-Xing
Published: February 2022

In this work, we study the resonance contributions to the decay $$B^-\rightarrow K^+K^-\pi ^-$$

B
-

→

K
+

K
-

π
-

, which is dominated by the scalar $$f_0(980), K_0^*(1430)$$

f
0

(
980
)

,

K
0
∗

(
1430
)

, vector $$\rho (1450), \phi (1020), K^*(892)$$

ρ

(
1450
)

,
ϕ

(
1020
)

,

K
∗

(
892
)

and tensor $$f_2(1270)$$

f
2

(
1270
)

resonances. The three-body decay is reduced to various quasi two-body decays, where the B meson firstly decays into a resonance and a pion or a kaon, subsequently the resonance decays into the other two final-state mesons. The quasi two-body decays are calculated within the light-cone sum rule approach utilizing the leading twist B meson light-cone distribution amplitudes. Finally, the decay branching fraction contributions from each resonance is calculated. Some of them are compatible with experiment or previous theoretical works. Including the effects of non-resonant and final-state interactions, we also evaluate the total branching fraction.
Thermodynamics of Kerr-AdS black holes in the restricted phase space
Authors: Gao Zeyuan , Kong Xiangqing , Zhao Liu
Published: February 2022

The thermodynamics for Kerr-AdS black hole in four dimensions is revisited using the recently proposed restricted phase space formalism, which includes the central charge C of the dual CFT and the chemical potential $$\mu $$
μ
, but excludes the pressure and the conjugate volume, as thermodynamic variables. The Euler relation holds automatically, and the first order homogeneity of the mass and the zeroth order homogeneity of the intensive variables are made explicit. Thermodynamic processes involving each pair of conjugate variables are studied in some detail, with emphasis on the scaling properties of the equations of states. It turns out that the thermodynamic behavior of the Kerr-AdS black hole is very similar to that of the RN-AdS black hole studied earlier. In particular, it is found that, there is a first order supercritical phase equilibrium in the $$T-S$$

T
-
S

processes at fixed nonvanishing angular momentum, while at vanishing angular momentum or at fixed angular velocities, there is always a non-equilibrium transition from a small unstable black hole state to a large stable black hole state. Moreover, there is a Hawking–Page phase transition in the $$\mu -C$$

μ
-
C

processes. Due to the complicatedness of the Kerr metric, the exact critical point and the Hawking–Page temperature are worked out explicitly only in the slow rotating limit, however the characteristic thermodynamic properties do not rely on the slow rotating approximation.
Relativistic calculations of two-color two-photon K-shell ionization
Authors: Fan J. , Hofbrucker J. , Volotka A. V. , Fritzsche S.
Published: February 2022

We investigate the two-color two-photon K-shell ionization of neutral atoms based on the relativistic second-order perturbation theory and independent particle approximation. Analytical expressions for the relativistic and nonrelativistic total cross sections are derived in terms of radial transition amplitudes and Stokes parameters. Particular attention is paid especially to how the two-photon ionization total cross section depends on the energy sharing and polarization of the two incident photons. We construct the nonrelativistic expressions of cross section ratios for different polarization combinations of the two incident photons. The numerical results of total cross section and cross section ratios show that the energy sharing of the two incident photons plays an essential role in two-photon K-shell ionization. Particularly, if the energies of the two incident photons are identical, the total cross section and cross section ratios will reach the minimum or maximum value. Moreover, due to the strong screening effects, we find strong deviations of the cross section ratios near the two-photon ionization threshold of the Ne atom.

Graphical abstract
A robust prediction from a minimal model of COVID-19 — Can we avoid the third wave?
Authors: Chowdhury Sourav , Roychowdhury Suparna , Chaudhuri Indranath
Published: February 2022

COVID-19 pandemic is one of the major disasters that humanity has ever faced. In this paper, we try to model the effect of vaccination in controlling the pandemic, particularly in context to the third wave which is predicted to hit globally. Here, we have modified the susceptible–exposed–infected–recovered–dead model by introducing a vaccination term. One of our main assumptions is that the infection rate ([Formula: see text]) is oscillatory. This oscillatory nature has been discussed earlier in literature with reference to the seasonality of epidemics. However, in our case, we invoke this nature of the infection rate ([Formula: see text]) to model the cyclical behavior of the COVID-19 pandemic within a short period. This study focuses on a minimalistic approach where we have logically deduced that the infection rate ([Formula: see text]) and the vaccination rate ([Formula: see text]) are the most important parameters while the other parameters can be assumed to be constants throughout the simulation. Finally, we have studied the rich interplay between the infection rate ([Formula: see text]) and the vaccination rate ([Formula: see text]) on the infectious cases of COVID-19 and made some robust conclusions regarding the global behavior of this pandemic in near future.
Efficacy and Safety of Chinese Medicine for COVID-19: A Systematic Review and Meta-Analysis
Authors: Wu Hanting , Dai Rongchen , Wu Xiaqiu , Li Qiushuang , Lu Hanti , Yang Junchao , Mao Wei , Hei Peijie , Liang Juan , Ji Conghua
Published: February 2022

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of traditional Chinese medicine for COVID-19 treatment with a focus on the benefits of symptomatic relief and time-related indexes. Seven electronic databases (PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data, and Chinese Clinical Trial Registry) were systematically searched from their beginning to April 2021. Only randomized controlled trials (RCTs) comparing patients using Western therapy (WT) alone and those using additional Chinese medicine (WT [Formula: see text] CM) were included. Primary outcomes included overall efficacy, lung recovery, and time to viral assay conversion. Secondary outcomes included time and rate of individual symptom recovery, laboratory indicators, and adverse events. Overall, 15 RCTs, including 1469 participants, were included in this review. WT [Formula: see text] CM significantly improved overall efficacy (risk ratio, RR [Formula: see text] 1.21; 95% CI: 1.12 to 1.30; [Formula: see text] [Formula: see text] 0.01) and lung recovery (RR [Formula: see text] 1.30; 95% CI:1.19 to 1.42; [Formula: see text] [Formula: see text] 0.01) and shortened the time to viral assay conversion (weighted mean differences, WMD [Formula: see text]1.38; 95% CI: −1.98 to −0.78; [Formula: see text] [Formula: see text] 0.01) and duration of chest distress (WMD [Formula: see text] 2.41; 95% CI: −2.99 to −1.83; [Formula: see text] [Formula: see text] 0.01) compared to WT alone. There was no difference in safety between the WT [Formula: see text] CM and WT groups (RR [Formula: see text] 0.94; 95% CI: 0.64 to 1.39; [Formula: see text] 0.76). In conclusion, the synthesized evidence from 15 RCTs showed that additional Chinese medication may improve treatment efficacy, relieve symptoms, promote lung recovery, and reduce the inflammatory response against COVID-19, while not increasing the risk of adverse events compared with conventional Western medication alone.
Osthole Exerts Inhibitory Effects on Hypoxic Colon Cancer Cells via EIF2α Phosphorylation-mediated Apoptosis and Regulation of HIF-1α
Authors: Peng Kui-Yuan , Chou Tz-Chong
Published: February 2022

Hypoxic microenvironment and dysregulated endoplasmic reticulum stress/unfolded protein response (UPR) system are considered important factors that promote cancer progression. Although osthole extracted from Cnidium monnieri(Fructus Cnidii) has been confirmed to exhibit an anticancer activity in various cancers, the effects of osthole in hypoxic colon cancer cells have not been explored. Therefore, the aim of this study was to examine whether osthole has an inhibitory effect on hypoxic colon cancer HCT116 cells and further investigate the underlying molecular mechanisms. Treatment with osthole significantly attenuated the cell viability, proliferation, and migration in hypoxic HCT116 cells. Osthole also activated UPR signaling such as phospho-eukaryotic initiation factor 2 alpha (EIF2[Formula: see text]/ATF4/CHOP/DR5 cascade accompanied by upregulation of pro-apoptotic proteins. Moreover, the tubule-like formation of human umbilical vein endothelial cells, the secretion of vascular endothelial growth factor A, and the expression and activity of hypoxia-inducible factor-1[Formula: see text] (HIF-1[Formula: see text] in hypoxic HCT116 cells were markedly suppressed by osthole. However, suppressing EIF2[Formula: see text] phosphorylation with salubrinal or ISRIB markedly reversed the effects of osthole on the expressions of pro-apoptotic proteins and HIF-1[Formula: see text]. Co-treatment of hypoxic HCT116 cells with osthole greatly increased the sensitivity to cisplatin and the expressions of phospho-EIF2[Formula: see text] and cleaved caspase 3. Collectively, the inhibitory effect of osthole in hypoxic HCT116 cells may be associated with EIF2[Formula: see text] phosphorylation-mediated apoptosis and translational repression of HIF-1[Formula: see text]. Taken together, osthole may be a potential agent in the treatment of colon cancer.
Study on the existence of tracking model for a d-dimensional random walk transportation radionuclide particle in a fractured medium
Authors: El-Hadidy Mohamed Abd Allah
Published: February 2022

This paper presents a novel tracking model to detect a [Formula: see text]-dimensional random walk radionuclides and toxic chemicals in a fractured medium with minimum time and maximum probability. This model improves the physical and chemical properties of a fractured medium for a long time. It depends on a coordinated search technique with multiple sensors. The radionuclide particle has a linear flows on one direction from [Formula: see text]-directions to spread. We consider this particle dispersed through a cylinder path in a very small time. The tracking or searching process in each cylinder path will be done by two sensors which start from any point in the fractured medium (space). The particle’s initial position is a vector of random variables with a known probability distribution. More than presenting the analytical solution which shows the existence of a finite tracking technique, we derive some auxiliary results related to optimal tracking technique. Besides that, we derive this optimal tracking technique which minimizes the expected value of the first meeting time between one of the sensors and the radionuclide or the toxic chemical particle. The effectiveness of this model appears in some numerical results.
Research on the structure of cosmic-ray electron and positron fluxes in GeV–TeV energy range
Authors: Zheng Zechun , Cui Zhiyi , Ruan Jianhong
Published: February 2022

The positron–electron fluxes detected by AMS02, CALET, DAMPE and Fermi-LAT have shown their complex structure which deviated from a single power-law, and the results of DAMPE and Fermi-LAT are obviously higher than those of AMS02 and CALET in 100[Formula: see text]GeV–1[Formula: see text]TeV range. We point out that the complex positron–electron flux structures can be attributed to two sources with a natural background, and the difference between the two groups of data can be explained in an anomalous bremsstrahlung theory.
FRACTAL-BASED MODEL FOR EVALUATING THE FILTRATION EFFICIENCY OF THE NON-WOVEN FIBROUS COMPOSITES
Authors: CHAO XUJIANG , JIANG DINGYI , WEI XIN , LIANG FEI , GU YUHENG , SHOU DAHUA
Published: February 2022

The classic single-fiber efficiency model based on ordered packing of fiber composites has been widely used to predict filtration efficiency of fibrous filters for 40 years. However, the simplified single-fiber model often overestimates the filtration efficiency as most fibrous composite filters are composed of randomly distributed fibers. The numerical methods have been successfully employed to re-construct the realistic fiber composites, but simulation of the multi-mechanism filtration process in the complex fibrous architecture is computationally expensive and case-based and derivation of a compact versatile model for broad applications remain challenging. In this work, a fractal-based homogenization model is developed to predict the filtration efficiency of the fibrous composites, by considering the spatially randomly distributed fibers and the quasi-random distribution of pore size. A comparison with available experimental results collected from references shows that the proposed model is of high accuracy in predicting the filtration of submicron aerosol particles. The calculated results show that the Kuwabara hydrodynamic factor is sensitive to the pore fractal dimension. The filtration efficiency for different particle diameters can be divided into three stages, which increase as the proportion of fibers warped by the fluid decreases. In addition, the total efficiency decreases with the increasing pore fractal dimension in a nonlinear trend. For the given fractal dimension, the filtration efficiency increases with the increase of pore size ratio, indicating that the more uniform the pore size distribution, the higher the efficiency.
A UNIFIED THREE-DIMENSIONAL EXTENDED FRACTIONAL ANALYTICAL SOLUTION FOR AIR POLLUTANTS DISPERSION
Authors: SYLVAIN TANKOU TAGNE ALAIN , PATRICE ELE ABIAMA , MARIE EMA’A EMA’A JEAN , PIERRE OWONO ATEBA , HUBERT BEN-BOLIE GERMAIN
Published: February 2022

A novel technique is presented to analytically solve the fractional diffusion equation for non-reactive air pollutants emitted from an elevated continuous source into the air. A generalized methodical solution combining first-order Wentzel–Kramers–Brillouin (WKB) approximation theory and the Sturm–Liouville problem is used to solve the air pollutants’ fractional dispersion equation. Drawing insight from previous analysis, we expanded the initial issue assuming the turbulent flow characteristics appearing in the diffusion process in a non-integer dimensional space. We solved the transformed problem and compared the solutions against data from real experiment. Physical consequences connecting to the conventional generalized diffusion equations are presented. The results indicate that the present solutions are in accordance with those obtained in literature. This report demonstrates that fractional equations can be applied in a practical prediction of pollutant dissemination in a turbulent atmosphere.