bluuebunny/crossref_metadata_2025 huggingface dataset:
Giving birth in the Murrumbidgee region: A quantitative and qualitative approach to general practice obstetrics in a rural region
Authors: Telford Megan , Harding Catherine , Stewart Ian , McGirr Joe , Seal Alexa
Published: April 2022

Objective

There is public concern regarding rural workforce shortages and closure of smaller obstetric centres.

Aim

To identify whether safety is a concern for Murrumbidgee hospitals that fit primary medical care models and ascertain general practitioner (GP) obstetricians’ perspectives regarding the benefits and challenges to practising in the region.

Design

Mixed‐method retrospective analysis of selected outcomes in the NSW Mothers and Babies Reports 2012–2015 and semi‐structured interviews with GP obstetricians.

Setting

Murrumbidgee Local Health District.

Main outcome measures

Evaluation of the safety of smaller hospitals (i.e. discharge status at birth, neonatal resuscitation and admission to intensive care); and iterative thematic analysis.

Results

This study provides evidence that smaller hospitals are providing safe obstetric care. Fewer babies were transferred, with fewer stillbirths, at the smaller hospitals and no difference in newborn deaths. There were more normal vaginal births in the smaller hospitals (70.0%) than in Wagga Wagga Base Hospital (57.2%) or Griffith Base Hospital (58.6%). There were fewer neonatal resuscitations in the smaller hospitals than in Wagga Wagga Base Hospital or Griffith Base Hospital. More than one‐quarter of babies were admitted into the special care/neonatal intensive care for both Wagga Wagga and Griffith Base Hospitals; however, the rate was <3% in the smaller hospitals (p < 0.001). GPs were overwhelmingly positive about the professional rewards of GP obstetric practice and the importance of continuity of care, despite barriers such as workforce shortages, loss of facilities and other staff (midwives and anaesthetists). Possible solutions included fostering support systems, proactive succession planning and improving training support.

Conclusions

GP obstetricians are providing a valuable, safe service in MLHD with both personal and community benefits.
Can double‐effect reasoning justify lethal organ donation?
Authors: Omelianchuk Adam
Published: April 2022

The dead donor rule (DDR) prohibits retrieval protocols that would be lethal to the donor. Some argue that compliance with it can be maintained by satisfying the requirements of double‐effect reasoning (DER). If successful, one could support organ donation without reference to the definition of death while being faithful to an ethic that prohibits intentionally killing innocent human life. On the contrary, I argue that DER cannot make lethal organ donation compatible with the DDR, because there are plausible ways it fails DER's requirements. A key takeaway is that the theories of intention and proportionality assumed in DER matter for its plausibility as a constraint on practical reasoning.
Can “My Body, My Choice” anti‐vaxxers be pro‐life?
Authors: Rulli Tina , Campbell Stephen
Published: April 2022

Many “anti‐vaxxers” oppose COVID‐19 vaccination mandates on the grounds that they wrongfully infringe on bodily autonomy. Their view has been expressed with the slogan “My Body, My Choice,” co‐opted from the pro‐choice abortion rights movement. Yet, many of those same people are pro‐life and support abortion restrictions that are effectively a kind of gestation mandate. Both vaccine and gestation mandates impose restrictions on bodily autonomy in order to prevent serious harms. This article evaluates the defensibility of the anti‐vax pro‐life position. We argue that the case for opposing gestation mandates on grounds of bodily autonomy is much stronger than the case for opposing vaccine mandates—even if fetuses have full moral status. Thus, there is a deep tension in being a pro‐life, COVID anti‐vaxxer concerned with bodily autonomy.
Outcomes of daratumumab in the treatment of multiple myeloma: A retrospective cohort study from the Canadian Myeloma Research Group Database
Authors: LeBlanc Richard , Mian Hira , Reece Donna , Masih‐Khan Esther , Kardjadj Moustafa , Jimenez‐Zepeda Victor H. , McCurdy Arleigh , Song Kevin , Sebag Michael , Louzada Martha , White Darrell , Stakiw Julie , Kotb Rami , Reiman Anthony , Aslam Muhammad , Gul Engin , Venner Christopher P.
Published: April 2022

Daratumumab (dara) has significantly altered the therapeutic landscape of multiple myeloma (MM), especially in the relapsed setting. This study aimed to evaluate the outcomes of dara‐containing regimens in the Canadian real‐world setting among relapsed and refractory MM available within the national Canadian Myeloma Research Group Database (CMRG‐DB). A total of 583 MM patients who received dara‐based therapy in second‐line or later treatment were included. After a median follow‐up of 17.5 months, the median progression‐free survival (PFS) and overall survival (OS) for the entire cohort were 13.1 and 32.9 months, respectively. The median PFS and OS were 23.5 and 49.1 months in second‐line treatment and decreased to 12.8 and 43.0 months in third‐line and 7.0 and 20.5 months in fourth‐line treatment respectively. Dara in monotherapy with or without corticosteroids after a median of four prior lines of therapy resulted in a median PFS of 3.9 months and a median OS of 17.1 months. The addition of bortezomib, lenalidomide or pomalidomide to dara resulted in an improved median PFS and OS of 8.3 and 26.2 months; 26.8 and 43.0 months; and 9.7 and 31.4 months respectively. These retrospective data from the CMRG‐DB suggest that outcomes are superior when dara is used in combination and in earlier lines of treatment.
Does weight loss lead to improvement of dermatological conditions: what is the evidence?
Authors: Rout Arpita , Das Anupam
Published: April 2022

Obese and overweight individuals may have a wide spectrum of cutaneous features and can have more severe manifestations of multiple dermatological conditions. There have been multiple expert opinions on the role of weight loss, in the improvement of skin conditions. There have been few studies over the past decade evaluating the effects of exercise and other modes of weight reduction on various dermatoses such as psoriasis, acne vulgaris, hidradenitis suppurativa and acanthosis nigricans. In this review, we have attempted to provide a summary of the beneficial effects of weight loss on various dermatological conditions.
Lone parenthood in the COVID‐19 context: Israeli single gay fathers' perspective
Authors: Tsfati Maya , Segal‐Engelchin Dorit
Published: April 2022

This article focuses on Israeli single gay fathers, using the Stress Process Model (SPM) as a framework to investigate their fathering experiences during the COVID‐19 pandemic. Thematic analysis of 15 in‐depth semi‐structured interviews with Israeli single gay fathers during the third national lockdown revealed that their parenting experiences during the pandemic were shaped by both COVID‐related stress exposure and interpersonal resources, which the fathers viewed as interactive. These fathers described three main pandemic‐specific stressors: financial insecurity and workplace transformation, feelings of loneliness and isolation and health‐related fears. Our findings highlight the cumulative effects of these stressors on the fathers' well‐being. The fathers also described the ways in which their interpersonal resources (i.e., social networks and strengthened relationship with their children during the pandemic) facilitated their coping with the pandemic‐related stressors. The study highlights the need for social workers to recognize the emerging family forms and to broaden their approach to parents during a time of ongoing community crisis, by addressing the differential effects on parents in diverse family structures.
Gaussian Process for Radiance Functions on the Sphere
Authors: Marques R. , Bouville C. , Bouatouch K.
Published: April 2022

Efficient approximation of incident radiance functions from a set of samples is still an open problem in physically based rendering. Indeed, most of the computing power required to synthesize a photo‐realistic image is devoted to collecting samples of the incident radiance function, which are necessary to provide an estimate of the rendering equation solution. Due to the large number of samples required to reach a high‐quality estimate, this process is usually tedious and can take up to several days. In this paper, we focus on the problem of approximation of incident radiance functions on the sphere. To this end, we resort to a Gaussian Process (GP), a highly flexible function modelling tool, which has received little attention in rendering. We make an extensive analysis of the application of GPs to incident radiance functions, addressing crucial issues such as robust hyperparameter learning, or selecting the covariance function which better suits incident radiance functions. Our analysis is both theoretical and experimental. Furthermore, it provides a seamless connection between the original spherical domain and the spectral domain, on which we build to derive a method for fast computation and rotation of spherical harmonics coefficients.
Association of residual inflammatory risk with stroke recurrence in patients with acute ischaemic stroke or transient ischaemic attack
Authors: Liu Huihui , Wang Mengxing , Xiang Xianglong , Pan Yuesong , Li Jiejie , Meng Xia , Li Hao , Li Zixiao , Jing Jing , Wang Yongjun
Published: April 2022

Background and purpose

The aim was to explore the association of residual inflammatory risk (RIR) with stroke recurrence after an index acute ischaemic stroke or transient ischaemic attack.

Methods

This study was based on the Third China National Stroke Registry. A total of 5840 patients with two high sensitivity C‐reactive protein (hsCRP) measurements at baseline and at 3 months were included in the analysis. High RIR was defined as an hsCRP ≥3 mg/l. Patients were divided into four groups: persistent high RIR (first high then high hsCRP), attenuated RIR (first high then low hsCRP), increased RIR (first low then high hsCRP) and persistent low RIR (first low then low hsCRP). The primary outcome was new stroke onset during the 1‐year follow‐up. Secondary outcomes included composite vascular events, all‐cause mortality and poor functional outcome (modified Rankin Scale score 3–6).

Results

During the 1‐year follow‐up, 523 (9.0%) patients had stroke recurrence. Patients with persistent high RIR had an increased risk of stroke recurrence (hazard ratio with 95% confidence interval 1.39, 1.08–1.78), compared with those with persistent low RIR. Similar results were found for the outcome of composite vascular events, mortality and poor functional outcome. An increased risk of stroke recurrence was further found in patients with persistent high RIR and intracranial artery stenosis or large‐artery atherosclerosis stroke subtype.

Conclusions

In patients with acute ischaemic stroke or transient ischaemic attack, persistent high RIR increased the risks of 1‐year stroke recurrence, especially in those with intracranial artery stenosis or large‐artery atherosclerosis subtype, composite vascular events, mortality and poor functional outcome.
Therapeutic potentials of melatonin in the treatment of lymphoma: A review of current evidence
Authors: Moradian Farid , Pourhanifeh Mohammad Hossein , Mehrzadi Saeed , Karimi‐Behnagh Arman , Hosseinzadeh Azam
Published: April 2022

Hematological malignancies including leukemia, multiple myeloma, and lymphoma are known as leading causes of death around the world. Despite all developments in cancer management, current therapeutic methods are still relatively inefficient, leading to the heavy financial burdens for public health systems. Strategic attempts in clinical practice must be based on three serious goals including (1) increasing the efficacy of treatments and decreasing their side‐effects; (2) decreasing financial price of treatments and related morbidity and mortality rates; and (3) improving life quality and survival of affected patients. Melatonin, a multipotential neurohormone mainly secreted by the pineal gland, has recently been shown to play essential roles in the treatment of various human diseases. Moreover, it possesses anticancer impacts and acts through regulation of underlying cellular and molecular mechanisms. In this article, we review mechanistic roles and beneficial effects of melatonin against hematological cancers, especially lymphoma.
NMR and computational studies reveal novel aspects in molecular recognition of unsaturated fatty acids with non‐labelled serum albumin
Authors: Alexandri Eleni , Primikyri Alexandra , Papamokos Georgios , Venianakis Themistoklis , Gkalpinos Vasileios K. , Tzakos Andreas G. , Karydis‐Messinis Andreas , Moschovas Dimitrios , Avgeropoulos Apostolos , Gerothanassis Ioannis P.
Published: April 2022

An approach based on the combined use of saturation transfer difference (STD), Tr‐NOESY and Inter‐ligand NOEs for PHArmacophore Mapping (INPHARMA) NMR techniques and docking calculations is reported, for the first time, for mapping interactions and specific binding sites of caproleic acid (10 : 1 cis‐9), oleic acid (18 : 1 cis‐9), linoleic acid (18 : 2 cis‐9,12) and linolenic (18 : 3, cis‐9,12,15) free fatty acids (FFAs) with non‐labelled serum albumin (BSA/HSA). Significant negative inter‐ligand NOEs between the FFAs and the drugs ibuprofen and warfarin, through competition experiments, were observed. The inter‐ligand NOEs and docking calculations were interpreted in terms of competitive binding mode, the significant folding of the bis allylic region and the presence of two orientations of the FFAs in the warfarin binding site (FA7), due to two potential distinctive anchoring polar groups of amino acids. This conformational flexibility is the reason that, the location and conformational states of the FFAs in the binding site of warfarin could not be determined accurately, despite numerous available X‐ray structural studies. α‐Linolenic acid competes favourably with warfarin at the binding site FA7. Isothermal titration calorimetry experiments of the preformed HSA/α‐linolenic acid complex upon titration with warfarin show a significant reduction in the binding constant of warfarin, in very good agreement with NMR and computational data. The combined use, therefore, of STD, Tr‐NOESY and INPHARMA NMR, ITC and docking calculations may find promising applications in the field of protein–lipid recognition research.
The micromechanics‐based rate‐dependent constitutive model of flawed rocks at intermediate strain rate
Authors: Zhou Xiaoping , Yang Haiqing , Berto Filippo
Published: April 2022

In the previous works conducted by Zhou and Yang, the deformation induced by wing crack coalescence was not investigated. In this paper, a novel micromechanics‐based rate‐dependent constitutive model is proposed to investigate the effect of wing crack coalescence on the mechanical properties of rocks at intermediate strain rate. The rate‐dependent damage mechanism is revealed using the frictional sliding crack model. Wing crack interaction is defined using pseudo‐traction method as well as the dynamic stress intensity factors. Strain energy density factor approach is applied to determine the critical condition of wing crack initiation, propagation, and coalescence. The strain softening behaviors of flawed rocks is studied by using thermodynamic theory.
Resist‐accept‐direct (RAD) considerations for climate change adaptation in fisheries: The Wisconsin experience
Authors: Feiner Zachary S. , Shultz Aaron D. , Sass Greg G. , Trudeau Ashley , Mitro Matthew G. , Dassow Colin J. , Latzka Alexander W. , Isermann Daniel A. , Maitland Bryan M. , Homola Jared J. , Embke Holly S. , Preul Michael
Published: April 2022

Decision‐makers in inland fisheries management must balance ecologically and socially palatable objectives for ecosystem services within financial or physical constraints. Climate change has transformed the potential range of ecosystem services available. The Resist‐Accept‐Direct (RAD) framework offers a foundation for responding to climate‐induced ecosystem modification; however, ecosystem trajectories and current practices must be understood to improve future decisions. Using Wisconsin's diverse inland fisheries as a case study, management strategies for recreational and subsistence fisheries in response to climate change were reviewed within the RAD framework. Current strategies largely focus on resist actions, while future strategies may need to shift toward accept or direct actions. A participatory adaptive management framework and co‐production of policies between state and tribal agencies could prioritise lakes for appropriate management action, with the goal of providing a landscape of diverse fishing opportunities. This knowledge co‐production represents a process of social learning requiring substantial investments of funding and time.
Gastric organoids: Advancing the study of H. pylori pathogenesis and inflammation
Authors: Idowu Sulaimon , Bertrand Paul P. , Walduck Anna K.
Published: April 2022

For decades, traditional in vitro and in vivo models used for the study of Helicobacter pylori infection have relied heavily on the use of gastric cancer cell lines and rodents. Major challenges faced by these methods have been the inability to study cancer initiation in already cancerous cell lines, and the difficulty in translating results obtained in animal models due to genetic differences. These challenges have prevented a thorough understanding of the pathogenesis of disease and slowed the development of cancer therapies and a suitable vaccine against the pathogen. In recent years, the development of gastric organoids has provided great advantages over the traditional in vivo and in vitro models due to their similarities to the human stomach in vivo, their ease of use, and the capacity for long‐term culture. This review discusses the advantages and limitations of existing in vivo and in vitro models of H. pylori infection, and how gastric organoids have been applied to study H. pylori pathogenesis, with a focus on how the pathogen interacts with the gastric epithelium, inflammatory processes, epithelial repair, and cancer initiation. The potential applications of organoids to address more complex questions on the role of hormones, vaccine‐induced immunity are also discussed.
THE INTERGENERATIONAL MORTALITY TRADE‐OFF OF COVID‐19 LOCKDOWN POLICIES
Authors: Ma Lin , Shapira Gil , de Walque Damien , Do Quy‐Toan , Friedman Jed , Levchenko Andrei A.
Published: April 2022

In lower‐income countries, the economic contractions that accompany lockdowns to contain COVID‐19 transmission can increase child mortality, counteracting the mortality reductions achieved by the lockdown. To formalize and quantify this effect, we build a macrosusceptible‐infected‐recovered model that features heterogeneous agents and a country‐group‐specific relationship between economic downturns and child mortality and calibrate it to data for 85 countries across all income levels. We find that in some low‐income countries, a lockdown can produce net increases in mortality. The optimal lockdown that maximizes the present value of aggregate social welfare is shorter and milder in poorer countries than in rich ones.
Effects of oxide addition on structure and properties of WC–10Co cemented carbide obtained by in situ synthesized powder
Authors: Deng Xiao‐Chun , Wang Kai‐Fei , Zhang Guo‐Hua
Published: April 2022

Combining spray drying and in situ synthesized technology, WC–10Co cemented carbide with uniform composition was prepared by vacuum sintering. The effects of Al2O3 and additions of different rare‐earth oxides (La2O3, Y2O3 and CeO2) on the microstructure and mechanical properties of WC–10Co were investigated. As the Al2O3 content increased from .5 to 2 wt%, the hardness of the sintered sample increased, whereas the relative density and fracture toughness decreased. Compared with the addition of .5 wt% Al2O3, the WC–10Co alloy with .5 wt% rare‐earth oxides had higher hardness. In addition, compared with the alloy without an inhibitor (.80 μm), after adding .5 wt% Al2O3, La2O3, Y2O3 and CeO2, the WC grain sizes were reduced to .73, .65, .71 and .62 μm, respectively, which indicated that the addition of Al2O3 and rare‐earth oxides could refine WC grain during sintering. Among these additives, CeO2 had the best effect. With the addition of .5 wt% CeO2, the hardness and the fracture toughness increased from 1299 to 1710 HV30 and from 16.18 to 18.90 MPa m1/2, respectively.
The prevalence and influencing factors for compassion fatigue among nurses in Fangcang shelter hospitals: A cross‐sectional study
Authors: Zhan Yuxin , Liu Yunfang , Chen Yi , Liu Huan , Zhang Wenya , Yan Rong , Yu Jiaohua , Li Suyun
Published: April 2022

Aim

We aim to investigate the prevalence and associated factors for compassion fatigue among nurses in Fangcang Shelter Hospitals in Wuhan. Studies have shown that compassion fatigue was more common among nurses than other health‐care providers, and its predictors were also different. In recent years, most studies have investigated compassion fatigue in emergency and oncology nurses, whereas there is little information on compassion fatigue among nurses from the frontline of Fangcang Shelter Hospitals during the COVID‐19 pandemic.

Methods

A descriptive, cross‐sectional design was used in this study. An online survey was conducted among nurses (n = 972) of five Fangcang Shelter Hospitals in Wuhan, Hubei province, China, from 6 March to 10 March 2020. A self‐administered questionnaire including demographic information, work‐related information, General Health Questionnaire, Perceived Stress Scale and Compassion Fatigue Scale was used.

Results

The prevalence of compassion fatigue among nurses in Fangcang Shelter Hospitals was moderate, and most cases were mild. There was a significant relationship between compassion fatigue and work‐related factors, mental health and perceived stress among nurses working in Fangcang Shelter Hospitals.

Conclusions

Various factors contribute to compassion fatigue, including lower job satisfaction and job adaptability, less praise from patients, more fear of infection and more perceived stress. A good working atmosphere, organizational support and psychological consultation are essential to alleviate nurses' compassion fatigue during the anti‐epidemic period.
The attitudes of young citizens in higher education towards universal basic income in the context of automation—A qualitative study
Authors: Herke Boglárka , Vicsek Lilla
Published: April 2022

One of the primary reasons for introducing the discussion about universal basic income (UBI) into political debate was to understand whether UBI could serve a good response to the negative consequences of technology‐driven job replacement. It is also a question whether citizens would accept UBI. Based on 30 interviews with Hungarian university students, we investigate the attitudes of young citizens to the introduction of UBI in a hypothetical scenario, situated in 2060, when technological unemployment is high. Interviewees expressed optimistic views about the future labour market and dismissed the scenario, preferring the option of job‐creation. Students claimed that people would become useless members of society by not working, which argument echoes the Hungarian government's discourse about the need for work‐based society. Students also stressed that work gives meaning to life. These narratives show a traditional understanding of work that might inhibit advocates from increasing social support for UBI.
Biotyping, virulotyping and biofilm formation ability of ESBL-Klebsiella pneumoniae isolates from nosocomial infections
Authors: Ahmed Heba A. , Ibrahim Eman H. S. , Abdelhaliem Ekram , Elariny Eman Y. T.
Published: April 2022

The aim of this study was to investigate the frequency, molecular characterization, virulence genes, resistance genes and antimicrobial profile of nosocomial extended spectrum beta lactamase producing Klebsiella species. A total of 22 (12.2%) K. pneumoniae strains were isolated from 180 clinical samples collected from hospitalized patients in Egypt. K. pneumoniae biotypes were B1 (72.8%), B3 (13.6%) and B4 (13.6%). The isolates were classified for the capsular serotypes, 86.4% (20/22) were of K1 serotype, while only two isolates (13.64%) were of K2 serotype. Hypermucoviscous K. pneumoniae isolates accounted for 68.2%. Biofilm formation ability of K. pneumoniae was determined by microtitre plate method. The majority of the isolates (40.9%) were moderate biofilm producers, while 27.3% were strong biofilm producers. All K. pneumoniae strains were positive for fimH and traT genes, while magA was identified in only 63.6% of the isolates. The antibiotic susceptibility profile of the isolates (n = 22) was determined by the disc diffusion technique using 23 different antibiotics. Streptomycin and imipenem are the most effective antibiotics against 22 tested K. pneumoniae isolates with sensitivity rates of 63.64% and 54.54% respectively. All tested K. pneumoniae isolates showed high resistance to amoxicillin∕clavulanate (100%), cefuroxime (100%) and ceftazidime (95.45%). Extended spectrum beta lactamases (ESBL) production and the presence of ESBL-related genes were tested in the isolates. All the isolates tested positive for blaVIM, NDM1 and blaTEM, while only 81.8 %tested positive for the blaSHV gene. Increasing antimicrobial resistance in K. pneumoniae causing nosocomial infections limits the use of antimicrobial agents for treatment. Furthermore, the spread of biofilm, multiple drug resistant and ESBL-producing K. pneumoniae isolates is a public threat for hospitalized patients.
Priming with biocides: A pathway to antibiotic resistance?
Authors: Adkin Pat , Hitchcock Andrew , Smith Laura J. , Walsh Susannah E.
Published: April 2022

Aims

To investigate the priming effects of sub-inhibitory concentrations of biocides on antibiotic resistance in bacteria.

Methods and results

Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were exposed to sub-inhibitory concentrations of biocides via a gradient plate method. Minimum inhibitory concentration (MIC) and antibiotic susceptibility were determined, and efflux pump inhibitors (thioridazine and chlorpromazine) were used to investigate antibiotic resistance mechanism(s). Escherichia coli displayed a twofold increase in MIC (32–64 mg l−1) to H2O2 which was stable after 15 passages, but lost after 6 weeks, and P. aeruginosa displayed a twofold increase in MIC (64–128 mg l−1) to BZK which was also stable for 15 passages. There were no other tolerances observed to biocides in E. coli, P. aeruginosa or S. aureus; however, stable cross-resistance to antibiotics was observed in the absence of a stable increased tolerance to biocides. Sixfold increases in MIC to cephalothin and fourfold to ceftriaxone and ampicillin were observed in hydrogen peroxide primed E. coli. Chlorhexidine primed S. aureus showed a fourfold increase in MIC to oxacillin, and glutaraldehyde-primed P. aeruginosa showed fourfold (sulphatriad) and eightfold (ciprofloxacin) increases in MIC. Thioridazine increased the susceptibility of E. coli to cephalothin and cefoxitin by fourfold and twofold, respectively, and both thioridazine and chlorpromazine increased the susceptibility S. aureus to oxacillin by eightfold and fourfold, respectively.

Conclusions

These findings demonstrate that sub-inhibitory concentrations of biocides can prime bacteria to become resistant to antibiotics even in the absence of stable biocide tolerance and suggests activation of efflux mechanisms may be a contributory factor.

Significance and Impact of the Study

This study demonstrates the effects of low-level exposure of biocides (priming) on antibiotic resistance even in the absence of obvious increased biocidal tolerance.
Perillaldehyde mitigates virulence factors and biofilm formation of Pseudomonas aeruginosa clinical isolates, by acting on the quorum sensing mechanism in vitro
Authors: Benny Anjitha Theres , Rathinam Prasanth , Dev Sanal , Mathew Bijo , Radhakrishnan Ethiraj K.
Published: April 2022

Aim

The incidence of biofilm linked catheter-associated urinary tract infections is increasing worldwide and Pseudomonas aeruginosa is one of the major causes. Perillaldehyde (PLD): as a natural, widely used flavouring agent, has been reported to possess various pharmacological properties. We hypothesized that PLD can inhibit biofilm formation and virulence factor (VF) production by P. aeruginosa by hampering the quorum sensing (QS) system(s).

Methods and Results

Minimum inhibitory concentration (MIC) of PLD was assessed for standard strain and two multi-drug resistant catheter isolates of P. aeruginosa utilizing the microdilution method. Microtiter plate assay, crystal violet staining and scanning electron microscopy were used to evaluate the biofilm inhibition property. CFU was utilized to assess the antifouling property of PLD. Detection of VFs and expression analysis of virulence determinants were applied to investigate the anti-virulence activity. Gene expression and molecular docking studies were also executed to explore the QS inhibition and binding of PLD with QS receptors. In the present study, PLD has significantly inhibited biofilm formation and antivirulence activity at sub-MIC levels (2.5 and 3.5 mM) in all the tested strains. In addition, molecular docking studies revealed a significant affinity towards QS receptors.

Discussions

Perillaldehyde, being a non-toxic food flavouring agent, significantly inhibited biofilm formation and exhibited antifouling property. PLD exhibited significantly reduced levels of VFs (p < 0.001) and their respective genetic determinants (p < 0.001). Gene expression analysis and molecular docking studies confirmed the interactions of PLD to the QS receptors, indicating the plausible mechanism for the anti-virulence property.

Significance and Impact of Study

This study identified the anti-virulence potential of PLD and provided mechanistic insights. PLD can be a suitable, non-toxic candidate for countering biofilms and associated pathogens, contributing to the prevention of biofilm-associated nosocomial infections.
The Power and Performance of ‘Association Bodies’ under the EU's Association Agreements with Georgia, Moldova and Ukraine
Authors: Tyushka Andriy
Published: April 2022

The growing number of EU bilateral agreements with non‐member states has led to a proliferation of transversal joint institutional frameworks governing them. The importance of joint bodies with their powers to oversee, facilitate and sometimes even enforce the implementation of agreements should not be underestimated. This particularly applies in cases where joint bodies are endowed with considerable decision‐making powers (for example, amendments to the agreement, binding decisions on furthering integration), as is the case with the ‘association bodies’ established in the 2010s under the EU's new‐generation association agreements with Georgia, Moldova and Ukraine. However, to date, the roles and performance of such joint bodies have been largely neglected. This article addresses this gap in the literature by providing a comparative law‐and‐politics account of institutional design, legal aspects of power conferral, and functional and performative aspects of authority exercised by these association bodies.
Intragastric injection of botulinum toxin A for weight loss: A systematic review and meta‐analysis of randomized controlled trials
Authors: Yen Yi‐An , Wang Chi‐Chih , Sung Wen‐Wei , Fang Kuan‐Chieh , Huang Shih‐Ming , Lin Chun‐Che , Tsai Ming‐Chang , Yang Tzu‐Wei
Published: April 2022

Background and Aim

Intragastric botulinum toxin A (BTA) injection is a potential treatment for weight reduction in obese patients. Current studies yielded conflicting results. We performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) to assess the efficacy of intragastric BTA injection for weight management.

Methods

We searched several databases to identify RCTs evaluating intragastric BTA injections for obesity. We applied random‐effects models for all meta‐analyses due to heterogeneity in the included studies. The mean difference (MD) and 95% confidence interval (CI) were calculated for continuous outcomes.

Results

A total of 6 RCTs including 192 subjects met the inclusion criteria and were included for the meta‐analysis. Although the pooled data from six studies showed no difference in the absolute weight loss between intragastric BTA injection and control, subgroup analysis showed a significantly decreased absolute weight after a BTA injection dose ≥ 200 U (MD, −2.04 kg; 95% CI, −3.96 to −0.12) and after multiple injection regions in the stomach combined with diet control (MD, −4.44 kg; 95% CI, −6.54 to −2.33 kg) compared with the control. Regarding absolute weight loss, the impact of endoscopic ultrasound‐guided injection and follow‐up duration showed no difference. Intragastric BTA injection had a significant change in body mass index (MD, −1.25 kg/m2; 95% CI, −2.18 to −0.32 kg/m2) and prolonged gastric half‐emptying time (MD, 11.37 min; 95% CI, −3.69 to 19.06 min).

Conclusion

Intragastric BTA injection is effective for obesity treatment, and adequate doses (≥ 200 U), multiple gastric injection regions, and combined diet control are crucial. However, given the small sample size and limited power, caution should be exercised.
Immunogenetics of gastrointestinal cancers: A systematic review and retrospective survey of inborn errors of immunity in humans
Authors: Zheng Beishi , Artin Michael G , Chung Howard , Chen Bing , Sun Siming , May Benjamin L , Hur Chin , Green Peter H R , Wang Timothy C , Park Jiheum , Kong Xiao‐Fei
Published: April 2022

Background and Aim

Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be associated with a potential risk factor for early‐onset gastrointestinal (GI) cancer.

Methods

We systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, and EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed. We also searched our institutional cancer registry for such cases.

Results

We identified 149 patients with both an IEI and a GI cancer, 95 presented gastric cancer, 13 small bowel cancer, 35 colorectal cancer, and 6 had an unspecified cancer or cancer at another site. Gastric and colon adenocarcinomas were the most common. For both gastric and colorectal cancers, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immunodeficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, and CTLA4. Impaired humoral immunity and Epstein–Barr virus (EBV) infection were frequently reported as factors potentially underlying early‐onset GI cancers in patients with IEIs. We identified one patient with CVID and early‐onset gastric adenocarcinoma, recurrent diarrhea, and gastrointestinal CMV infection from a retrospective survey.

Conclusion

Patients with IEIs should be considered at risk of early‐onset GI cancers and should therefore undergo cancer screening at an earlier age.
Localized delivery of curcumin by thermosensitive hydrogels for promoting wound healing
Authors: Zhang Zhigang , Chen Huiya , Shen Wanlu , Deng Juqing , Bai Chunling , Xiao Yun , Lyu Lechun
Published: April 2022

Background

Curcumin can promote wound healing, but its drug delivery medium needs to be improved further.

Objectives

A curcumin‐loaded thermosensitive hydrogel was prepared, its characterization was evaluated, and its promoting effect on wound healing was observed.

Methods

Curcumin‐loaded thermosensitive hydrogels were prepared with different percentages of poloxamer 188 and poloxamer 407. A small tube inversion assay was used to observe the sol‐gel transition temperature, and a rotational rheometer was used to detect the sol viscosity, sol‐gel phase transition temperature, and phase transition time. The microstructure of the gel was observed by scanning electron microscopy, and Fourier infrared spectroscopy was used to evaluate whether curcumin was successfully loaded. Finally, its promoting effect on wound healing was observed in vivo and in vitro.

Results

Poloxamer 407 24% and poloxamer 188 1% were selected to prepare curcumin‐loaded thermosensitive hydrogels. After 60 ± 15 s at 32°C, the sol‐gel transition process was completed, with certain elastic behavior and solid‐like rheological properties. Scanning electron microscopy showed that the pores of the curcumin‐P407/P188 thermosensitive hydrogel were interconnected, with an average pore size ranging from 5 to 10 μm. Hydrogels showed a higher swelling ratio. Fourier transform infrared spectroscopy showed that curcumin had been incorporated into the hydrogel. Live/dead cell assays suggested that the hydrogel was not toxic to fibroblasts. Curcumin‐loaded thermosensitive hydrogels can promote an increase in S‐phase fibroblasts and improve wound healing.

Conclusions

Curcumin‐loaded P407/P188 thermosensitive hydrogel improves wound healing. More in‐depth research is needed in the future.
Etiology distribution of abnormal uterine bleeding according to FIGO classification system: A combined study of ultrasound and histopathology
Authors: Ni Pingjuan , Wu Mei , Guan Hui , Yuan Yuqi , Zhang Lulu , Zhang Feixue , Wei Xiuliang , Li Ya
Published: April 2022

Aim

To classify the FIGO's PALM‐COEIN etiology for abnormal uterine bleeding (AUB) patients according to the ultrasound and histopathology and to evaluate the etiology prevalence distribution for AUB patients.

Methods

A total of 1065 women with AUB in the Second Hospital of Shandong University between January 2019 and March 2021. The intrauterine histopathological and ultrasound results were reviewed retrospectively.PALM‐COEIN etiology classification was performed according to histopathology and ultrasound. The classification system was stratified into nine basic categories: Polyp (AUB‐P), adenomyosis (AUB‐A), leiomyoma (AUB‐L), malignancy and hyperplasia (AUB‐M), coagulopathy (AUB‐C), ovulatory disorders (AUB‐O), endometrium (AUB‐E), Iatrogenic(AUB‐I), and not classified (AUB‐N). The number of cases and composition ratio were also calculated.

Results

According to the FIGO's classification system, the PALM group (656,61.60%), which were defined as structural entities that can be measured visually with ultrasound and/or histopathology. 176 (16.53%) patients were classified as AUB‐P,102 (9.58%) patients were classified as AUB‐A, 487(45.73%) patients were classified as AUB‐L, 31 (2.91%) patients were classified as AUB‐M. The COEIN group (409,38.40%), which were defined as nonstructural entities that cannot be measured by ultrasound and/or histopathology. Nobody were classified as AUB‐C in our group, and 383 (35.96%) patients were classified as AUB‐O, 4 (0.38%) patients were classified as AUB‐E,14 (1.31%) patients were classified as AUB‐I,8 (0.75%) patients were classified as AUB‐N.

Conclusion

In our study, AUB‐L was the most common cause, followed by AUB‐O, AUB‐P, AUB‐A, AUB‐M, AUB‐I, AUB‐N, and AUB‐E.PALM‐COEIN etiology classification system played an important role in the epidemic and management standardization of AUB patients, provided an effective communication between physicians and researchers also. Ultrasonography was the preferred examination for AUB patients, especially with structural abnormalities.
High‐dimensional sparse multivariate stochastic volatility models
Authors: Poignard Benjamin , Asai Manabu
Published: April 2022

Although multivariate stochastic volatility models usually produce more accurate forecasts compared with the MGARCH models, their estimation techniques such as Bayesian MCMC typically suffer from the curse of dimensionality. We propose a fast and efficient estimation approach for MSV based on a penalized OLS framework. Specifying the MSV model as a multivariate state‐space model, we carry out a two‐step penalized procedure. We provide the asymptotic properties of the two‐step estimator and the oracle property of the first‐step estimator when the number of parameters diverges. The performances of our method are illustrated through simulations and financial data. Supplementary Material presenting technical proofs is available online.
Metaphysics of the Bayesian mind
Authors: Tiehen Justin
Published: April 2022

Recent years have seen a Bayesian revolution in cognitive science. In this paper, I work out the implications of this revolution for the metaphysics of mind. My central claim is that the Bayesian approach supports a novel empirical argument for normativism, the thesis that belief has a rational normative essence. The argument I develop draws in part on the causal powers subset account of realization, with the connection being that Bayesians often appeal to Marr's framework of levels of analysis, which carries with it multiple realizability claims that can be understood in terms of the subset model.
Colonic volume in patients with functional constipation or irritable bowel syndrome determined by magnetic resonance imaging
Authors: Klinge Mette Winther , Krogh Klaus , Mark Esben Bolvig , Drewes Asbjørn Mohr , Brix Lau , Isaksen Christin , Dedelaite Milda , Frøkjær Jens Brøndum , Fynne Lotte Vinskov
Published: April 2022

Background

Functional constipation (FC) and irritable bowel syndrome constipation type (IBS‐C) share many similarities, and it remains unknown whether they are distinct entities or part of the same spectrum of disease. Magnetic resonance imaging (MRI) allows quantification of intraluminal fecal volume. We hypothesized that colonic volumes of patients with FC would be larger than those of patients with IBS‐C, and that both patient groups would have larger colonic volumes than healthy controls (HC).

Methods

Based on validated questionnaires, three groups of participants were classified into FC (n = 13), IBS‐C (n = 10), and HC (n = 19). The colonic volume of each subject was determined by MRI. Stool consistency was described by the Bristol stool scale and colonic transit times were assessed with radiopaque makers.

Key Results

Overall, total colonic volumes were different in the three groups, HC (median 629 ml, interquartile range (IQR)(562–868)), FC (864 ml, IQR(742–940)), and IBS‐C (520 ml IQR(489–593)) (p = 0.001). Patients with IBS‐C had lower colonic volumes than patients with FC (p = 0.001) and HC (p = 0.019), but there was no difference between FC and HC (p = 0.10). Stool consistency was similar in the two patient groups, but patients with FC had longer colonic transit time than those with IBS‐C (117.6 h versus 43.2 h,p = 0.019).

Conclusion

Patients with IBS‐C have lower total colonic volumes and shorter colonic transit times than patients with FC. Future studies are needed to confirm that colonic volume allows objective distinction between the two conditions.
LATERAL BRANCHING OXIDOREDUCTASE, one novel target gene of Squamosa Promoter Binding Protein‐like 2, regulates tillering in switchgrass
Authors: Yang Ruijuan , Liu Wenwen , Sun Ying , Sun Zhichao , Wu Zhenying , Wang Yamei , Wang Mengqi , Wang Honglun , Bai Shiqie , Fu Chunxiang
Published: April 2022

Strigolactones (SLs) play a critical role in regulating plant tiller number. LATERAL BRANCHING OXIDOREDUCTASE (LBO) encodes an important late‐acting enzyme for SL biosynthesis and regulates shoot branching in Arabidopsis. However, little is known about the function of LBO in monocots including switchgrass (Panicum virgatum L.), a dual‐purpose fodder and biofuel crop.

We studied the function of PvLBO via the genetic manipulation of its expression levels in both the wild‐type and miR156 overexpressing (miR156OE) switchgrass. Co‐expression analysis, quantitative real‐time polymerase chain reaction (qRT‐PCR), transient dual luciferase assay, and chromatin immunoprecipitation‐qPCR were all used to determine the activation of PvLBO by miR156‐targeted Squamosa Promoter Binding Protein‐like 2 (PvSPL2) in regulating tillering of switchgrass.

PvLBOtranscripts dramatically declined in miR156OE transgenic switchgrass, and the overexpression of PvLBO in the miR156OE transgenic line produce fewer tillers than the control. Furthermore, we found that PvSPL2 can directly bind to the promoter of PvLBO and activate its transcription, suggesting that PvLBO is a novel downstream gene of PvSPL2.

We propose that PvLBO functions as an SL biosynthetic gene to mediate tillering and acts as an important downstream factor in the crosstalk between the SL biosynthetic pathway and the miR156‐SPL module in switchgrass.
Comparative genomics reveals a dynamic genome evolution in the ectomycorrhizal milk‐cap (Lactarius) mushrooms
Authors: Lebreton Annie , Tang Nianwu , Kuo Alan , LaButti Kurt , Andreopoulos William , Drula Elodie , Miyauchi Shingo , Barry Kerrie , Clum Alicia , Lipzen Anna , Mousain Daniel , Ng Vivian , Wang Ran , Dai Yucheng , Henrissat Bernard , Grigoriev Igor V. , Guerin‐Laguette Alexis , Yu Fuqiang , Martin Francis M.
Published: April 2022

Ectomycorrhizal fungi play a key role in forests by establishing mutualistic symbioses with woody plants. Genome analyses have identified conserved symbiosis‐related traits among ectomycorrhizal fungal species, but the molecular mechanisms underlying host specificity remain poorly known.

We sequenced and compared the genomes of seven species of milk‐cap fungi (Lactarius, Russulales) with contrasting host specificity. We also compared these genomes with those of symbiotic and saprotrophic Russulales species, aiming to identify genes involved in their ecology and host specificity.

The size of Lactarius genomes is significantly larger than other Russulales species, owing to a massive accumulation of transposable elements and duplication of dispensable genes. As expected, their repertoire of genes coding for plant cell wall‐degrading enzymes is restricted, but they retained a substantial set of genes involved in microbial cell wall degradation. Notably, Lactarius species showed a striking expansion of genes encoding proteases, such as secreted ectomycorrhiza‐induced sedolisins. A high copy number of genes coding for small secreted LysM proteins and Lactarius‐specific lectins were detected, which may be linked to host specificity.

This study revealed a large diversity in the genome landscapes and gene repertoires within Russulaceae. The known host specificity of Lactarius symbionts may be related to mycorrhiza‐induced species‐specific genes, including secreted sedolisins.
Risk assessment based on a STPA–FMEA method: A case study of a sweeping robot
Authors: Zhang Yanxi , Liu Tiezhong
Published: April 2022

Despite rapid developments in the quality and safety of consumer products, the rise of intelligent household appliances, such as sweeping robots, has introduced new safety concerns. Considering “person–product–environment” elements and the complex systems of emerging consumer products, this study presents a new method of risk assessment for consumer products: systems theoretic process analysis (STPA)–failure mode and effects analysis (FMEA). As a case study, this method is applied to the safety control of a sweeping robot. The results suggest that this method can identify all the possible failure modes and injury scenarios among the product components, and the safety constraints in the hierarchical control structure of the interactive system. Moreover, the STPA–FMEA method combines user and environmental factors with the value of product risk events, based on the risk priority number (RPN). This provides an accurate and orderly system to reduce or eliminate the root causes of accidents and injuries. Finally, analysis of unsafe control behavior and its causes can be used to suggest improved safety constraints, which can effectively reduce the risk of some injury scenarios. This paper presents a new method of risk assessment for consumer products and a general five‐level complex index system.