bluuebunny/crossref_metadata_2025 huggingface dataset:
Well‐being of undergraduate dental students: Questionnaire design, findings and future directions
Authors: Chan Charlotte Cheuk Kwan , Fok Elise Hoi Wan , Lo Yan Ting Rosealeen , Ng Wing Yan , Botelho Michael George
Published: March 2024

Introduction

The recent pandemic has highlighted the importance of addressing well‐being in the overall health of students. There is a need for support systems within dental schools to help students demonstrate resilience, adapt to learning environments and thrive in their professional careers.

Objectives

The main aim of the study was to evaluate Bachelor of Dental Surgery (BDS) students' understanding and experience of well‐being. The objectives were to create a suitable survey to assess students' well‐being, investigate the factors affecting dental students' well‐being and develop a student well‐being action plan based on the analysis of the survey.

Methods

A literature review was conducted to identify and critically assess existing measures of well‐being in dental students. Four domains of well‐being (emotional, physical, social, intellectual) relevant to dental students were identified. Through a comprehensive iterative process, a two‐part survey was developed and tested, which measured individual experiences of well‐being across the four domains and collected feedback on proposed initiatives to support student well‐being. The survey was disseminated to all 452 dental students from Years 1 through 6, of which 71% (321) responded.

Results

The survey revealed low levels of overall well‐being among the dental student population, which worsened with increasing years of clinical study. Fear of failing exams presented the biggest challenge with regard to emotional well‐being, while sleep deprivation and occupational health hazards most affected the physical well‐being domain. Intellectual well‐being was compromised by insufficient free time to pursue extracurricular interests and concerns about achieving the required skills. Despite a majority experiencing positive relationships with their peers and tutors, less than a fifth agreed that the Faculty of Dentistry ‘supported my well‐being as a dental student’.

Conclusion

As the first investigation of the well‐being of dental students in Hong Kong, the key stressors identified were examinations, long schedules and the physical burden of dental work, which are consistent with international literature. The findings reveal students' needs and preferences for well‐being initiatives which will be optimized in the implementation of student‐centred curricular activities.
Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis
Authors: Meisel Andreas , Saccà Francesco , Spillane Jennifer , Vissing John ,   the MG Collegium Sub‐committee
Published: March 2024

Background

Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert‐derived consensus recommendations for good practice.

Methods

A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub‐committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence‐based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1–10.

Results

Eighteen expert‐ and evidence‐based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG‐ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State [PASS]) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG‐ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds.

Conclusions

This process provided evidence‐ and expert consensus‐based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients.
A novel pathological mutant reveals the role of torsional flexibility in the serpin breach in adoption of an aggregation‐prone intermediate
Authors: Kamuda Kamila , Ronzoni Riccardo , Majumdar Avik , Guan Fiona H. X. , Irving James A. , Lomas David A.
Published: March 2024

Mutants of alpha‐1‐antitrypsin cause the protein to self‐associate and form ordered aggregates (‘polymers’) that are retained within hepatocytes, resulting in a predisposition to the development of liver disease. The associated reduction in secretion, and for some mutants, impairment of function, leads to a failure to protect lung tissue against proteases released during the inflammatory response and an increased risk of emphysema. We report here a novel deficiency mutation (Gly192Cys), that we name the Sydney variant, identified in a patient in heterozygosity with the Z allele (Glu342Lys). Cellular analysis revealed that the novel variant was mostly retained as insoluble polymers within the endoplasmic reticulum. The basis for this behaviour was investigated using biophysical and structural techniques. The variant showed a 40% reduction in inhibitory activity and a reduced stability as assessed by thermal unfolding experiments. Polymerisation involves adoption of an aggregation‐prone intermediate and paradoxically the energy barrier for transition to this state was increased by 16% for the Gly192Cys variant with respect to the wild‐type protein. However, with activation to the intermediate state, polymerisation occurred at a 3.8‐fold faster rate overall. X‐ray crystallography provided two crystal structures of the Gly192Cys variant, revealing perturbation within the ‘breach’ region with Cys192 in two different orientations: in one structure it faces towards the hydrophobic core while in the second it is solvent‐exposed. This orientational heterogeneity was confirmed by PEGylation. These data show the critical role of the torsional freedom imparted by Gly192 in inhibitory activity and stability against polymerisation.
Unraveling the peculiarities and development of novel inhibitors of leishmanial arginyl‐tRNA synthetase
Authors: Nasim Fouzia , Kumar Muppidi Shravan , Alvala Mallika , Qureshi Insaf Ahmed
Published: March 2024

Aminoacylation by tRNA synthetase is a crucial part of protein synthesis and is widely recognized as a therapeutic target for drug development. Unlike the arginyl‐tRNA synthetases (ArgRSs) reported previously, here, we report an ArgRS of Leishmania donovani (LdArgRS) that can follow the canonical two‐step aminoacylation process. Since a previously uncharacterized insertion region is present within its catalytic domain, we implemented the splicing by overlap extension PCR (SOE–PCR) method to create a deletion mutant (ΔIns‐LdArgRS) devoid of this region to investigate its function. Notably, the purified LdArgRS and ΔIns‐LdArgRS exhibited different oligomeric states along with variations in their enzymatic activity. The full‐length protein showed better catalytic efficiency than ΔIns‐LdArgRS, and the insertion region was identified as the tRNA binding domain. In addition, a benzothiazolo‐coumarin derivative (Comp‐7j) possessing high pharmacokinetic properties was recognized as a competitive and more specific inhibitor of LdArgRS than its human counterpart. Removal of the insertion region altered the mode of inhibition for ΔIns‐LdArgRS and caused a reduction in the inhibitor's binding affinity. Both purified proteins depicted variances in the secondary structural content upon ligand binding and thus, thermostability. Apart from the trypanosomatid‐specific insertion and Rossmann fold motif, LdArgRS revealed typical structural characteristics of ArgRSs, and Comp‐7j was found to bind within the ATP binding pocket. Furthermore, the placement of tRNAArg near the insertion region enhanced the stability and compactness of LdArgRS compared to other ligands. This study thus reports a unique ArgRS with respect to catalytic as well as structural properties, which can be considered a plausible drug target for the derivation of novel anti‐leishmanial agents.
A probabilistic life prediction framework for vibration fatigue of turbine blade based on refined polynomial chaos expansion
Authors: Fang Jie , Liu Chengxuan , Li Kaiyang , Zou Shuang , Sun Bing , Li Yi
Published: March 2024

Vibration fatigue is a typical form of multiaxial fatigue. In this study, initial vibration fatigue tests were conducted on rocket turbine blades, and significant dispersion in fatigue life was found. Consistent with this finding, a novel probabilistic life prediction framework was proposed. This framework integrates sensitivity analysis and sequential sampling technology and introduces polynomial chaos expansion as a computationally efficient alternative to finite element analysis. And a continuous mechanics‐based damage evolution model was employed to examine the vibration fatigue life of turbine blades. The findings validate the effectiveness of the framework, as no significant difference was found between the experimental results and simulated predictions at the 95% confidence level. Furthermore, comparison with the Monte Carlo simulation indicated that this framework achieves comparable prediction accuracy, while significantly reducing the required samples by 2 orders of magnitude, which effectively addresses the fatigue problem of small sample data. This framework enables rapid and accurate multiaxial fatigue probabilistic life prediction, which holds important implications for the reliability design of reusable spacecraft.
A meshfree approach for analyzing strain fields near crack tips from Digital Image Correlation displacement data
Authors: Gómez Gonzales Giancarlo L. , Camacho‐Reyes Alonso , Ortiz González Julián A. , Díaz Francisco A.
Published: March 2024

The element‐free Galerkin (EFG) meshfree method is employed in this research to compute strain fields based on discrete displacement data obtained from digital image correlation (DIC). To validate the method's accuracy, both simulated images with highly heterogeneous deformations and real tests conducted on notched specimens with known solutions are initially employed. The study then investigates the strain field near the crack tip in an AISI 1020 steel specimen through a multiscale experiment. From the macroscale experiment, the strain data are used to determine the crack‐tip plastic zone size, and the solution is compared with predictions from linear‐elastic fracture mechanics. The stress intensity factor is also determined. Furthermore, the high strain gradient ahead of the crack tip is determined from the microscale experiment and compared against commercial DIC software. Experimental results confirm the effectiveness of the proposed formulation in crack tip analysis.
Neuralgia in the occipital region associated with ipsilateral trigeminal herpes zoster: Three case reports
Authors: Nakaya Akihiko , Kaneko Kimihiko , Miyazawa Koichi , Matsumoto Arifumi , Hisanaga Kinya , Matsumori Yasuhiko , Nagano Isao
Published: March 2024

Background

Nerve fibers related to pain and temperature sensation in the trigeminal nerve territory converge with the upper cervical spinal nerves from the level of the lower medulla oblongata to the upper cervical cord. This structure is called the trigemino‐cervical complex and may cause referred pain in the territory of the trigeminal or upper cervical spinal nerves.

Case Series

Here, we report three cases of paroxysmal neuralgia in the occipital region with mild conjunctivitis or a few reddish spots in the ipsilateral trigeminal nerve territory. The patients exhibited gradual progression of these reddish spots evolving into vesicles over the course of several days, despite the absence of a rash in the occipital region. The patients were diagnosed with trigeminal herpes zoster and subsequently received antiherpetic therapy. Remarkably, the neuralgia in the occipital region showed gradual amelioration or complete resolution before the treatment, with no sequelae reported in the occipital region.

Discussion

The trigemino‐cervical complex has the potential to cause neuralgia in the occipital region, as referred pain, caused by trigeminal herpes zoster. These cases suggest that, even if conjunctivitis or reddish spots appear to be trivial in the trigeminal nerve territory, trigeminal herpes zoster should be considered when neuralgia occurs in the ipsilateral occipital region.
Analysis of changes in high‐mobility group box 1, receptor for advanced glycation endproducts, and T helper 17/regulatory T balance in severe preeclampsia with acute heart failure
Authors: De Chen , Xuan Liang , jingjing Zhang , Honghong Zhang , Kun Zuo , Song Du , Yaqi Song , Ying Jiang , Cheng Cheng , Jian Liu
Published: March 2024

We measured the levels of High‐Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child‐care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme‐linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)‐17, IL‐6, transforming growth factor β (TGF‐β), IL‐10, and NT‐proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL‐17, and IL‐6 and was negatively correlated with TGF‐β and IL‐10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.
NEDD4L is a promoter for angiogenesis and cell proliferation in human umbilical vein endothelial cells
Authors: Liu Binghong , Song Fei , Zhou Xiaoxia , Wu Chan , Huang Huizhu , Wu Weiyin , Li Gang , Wang Yan
Published: March 2024

Dysregulated angiogenesis leads to neovascularization, which can promote or exacerbate various diseases. Previous studies have proved that NEDD4L plays an important role in hypertension and atherosclerosis. Hence, we hypothesized that NEDD4L may be a critical regulator of endothelial cell (EC) function. This study aimed to define the role of NEDD4L in regulating EC angiogenesis and elucidate their underlying mechanisms. Loss‐ and gain‐of‐function of NEDD4L detected the angiogenesis and mobility role in human umbilical vein endothelial cells (HUVECs) using Matrigel tube formation assay, cell proliferation and migration. Pharmacological pathway inhibitors and western blot were used to determine the underlying mechanism of NEDD4L‐regulated endothelial functions. Knockdown of NEDD4L suppressed tube formation, cell proliferation and cell migration in HUVECs, whereas NEDD4L overexpression promoted these functions. Moreover, NEDD4L‐regulated angiogenesis and cell progression are associated with the phosphorylation of Akt, Erk1/2 and eNOS and the expression of VEGFR2 and cyclin D1 and D3. Mechanically, further evidence was confirmed by using Akt blocker MK‐2206, Erk1/2 blocker U0126 and eNOS blocker L‐NAME. Overexpression NEDD4L‐promoted angiogenesis, cell migration and cell proliferation were restrained by these inhibitors. In addition, overexpression NEDD4L‐promoted cell cycle‐related proteins cyclin D1 and D3 were also suppressed by Akt blocker MK‐2206, Erk1/2 blocker U0126 and eNOS blocker L‐NAME. Our results demonstrated a novel finding that NEDD4L promotes angiogenesis and cell progression by regulating the Akt/Erk/eNOS pathways.
Water‐in‐oil adjuvant challenges in fish vaccination: An experimental inactivated adjuvanted vaccine against betanodavirus infection in Senegalese sole
Authors: Valero Yulema , Souto Sandra , Olveira José G. , López‐Vázquez Carmen , Dopazo Carlos P. , Bandín Isabel
Published: March 2024

The extensive growth of intensive fish farming has led to a massive spread of infectious diseases. Nervous necrosis virus (NNV) is the causative agent of the viral encephalo‐ and retinopathy disease which has become a major threat for fish farming all over the globe. The devastating mortality rates recorded in disease outbreaks, especially when infected specimens are at early stages of development, have a high economic impact on the sector. Currently, vaccines are the most cost‐effective preventing tool in the fight against viruses. Inactivated vaccines have the advantage of simplicity in their development at the same time as present the antigen in a similar manner than the natural infection in the host. Nevertheless, they usually trigger weaker immune responses needing adjuvants to boost their effectiveness. In this work, we have intraperitoneally vaccinated Senegalese sole juveniles (Solea senegalensis) with a previously designed inactivated vaccine against NNV based on binary ethylenimine (BEI), mixed or not with an oil‐adjuvant. Our results demonstrated the potential activation of different immune pathways when the vaccine was administered alone compared to the oil‐adjuvanted vaccine, both resulting in an equivalent partial improvement in survival following a NNV challenge. However, whilst the vaccine alone led to a significant increase in specific antibodies, in the adjuvanted version those antibodies were kept basal although with a slight improvement in their neutralization capacity. At transcriptional level, neither vaccine (adjuvanted or not) triggered the immune system activation during the vaccination period. However, after NNV infection, the BEI‐inactivated vaccines alone and oil‐adjuvanted both elicited the stimulation of antiviral responsive genes (rtp3, herc4), antigen presentation molecules (mhcii) and T‐cell markers (cd8a) in the head‐kidney. Additionally, the oil‐adjuvanted vaccine appears to stimulate mediator cytokines (il6) and B‐cell markers (ight and ighm). Surprisingly, when the adjuvant was administered alone, fish showed the highest survival rates concomitantly with a lack of NNV‐IgM production, pointing to the possible induction of different immune pathways than the B‐cell responses via antibodies by the adjuvant. Since this combined vaccine did not succeed in the full extension of protection against the pathogen, further studies should be performed focusing on unravelling the molecular mechanisms through which adjuvants trigger the immune response, both independently and when added to a vaccine antigen.
Prospective randomized double‐blind comparative study of topical acetyl zingerone with tetrahexyldecyl ascorbate versus tetrahexyldecyl ascorbate alone on facial photoaging
Authors: Afzal Nasima , Nguyen Nhi , Min Mildred , Egli Caitlin , Afzal Shabnam , Chaudhuri Ratan K. , Burney Waqas A. , Sivamani Raja K.
Published: March 2024

Background

Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging.

Aims

To examine the effects of THDA and AZ (THDA‐AZ) on skin photoaging compared to THDA alone.

Patients/Methods

In this double‐blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA‐AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self‐perception of skin and tolerability were assessed through questionnaires.

Results

Average wrinkle severity was significantly decreased in the THDA‐AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA‐AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA‐AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema.

Conclusions

Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both.
Prenatal insomnia disorder may predict concurrent and postpartum psychopathology: A longitudinal study
Authors: Palagini Laura , Miniati Mario , Driul Lorenza , Colizzi Marco , Comacchio Carla , Gemignani Angelo , Balestrieri Matteo ,   Insomnia in Pregnancy Research Group (IPRG)
Published: March 2024

While insomnia symptoms may be a risk factor for mental disturbances, few studies evaluated “Insomnia Disorder” and its relationship with perinatal psychopathology. Pregnant women were recruited during their last routine assessment before being hospitalized for delivery during the 3rd trimester at the Gynaecological Unit of the University Hospital of Ferrara and Udine, Italy, from January 2022 to January 2023. Our assessment included baseline evaluation (T0), and evaluations at 1 month (T1) and 3 months (T2) in the postpartum period, with specific questionnaires for insomnia disorder, such as Sleep Condition Indicator, mood and anxiety symptoms and psychosocial functioning, such as Edinburgh Postnatal Depression Scale, Mood Disorder Questionnaire, State–Trait Anxiety Inventory, Work and Social Adjustment Scale. At T0, 181 pregnant women were included. Insomnia disorder affected 22.3% at T0, 23.5% at T1 and 16.2% at T2. Women with insomnia disorder at baseline were significantly more affected by concurrent anxiety and depressive symptoms, had higher bipolar diathesis and poorer psychosocial functioning in the perinatal period. Prenatal insomnia disorder predicted anxiety (T0: odds ratio 4.44, p << 0.001; T1: odds ratio 4.009, p = 0.042) and depressive symptoms (T0: odds ratio 2.66, p = 0.015; T1: odds ratio 11.20, p = 0.001; T2: odds ratio 12.50 p = 0.049) in both the prenatal and postnatal period. It also predicted poor psychosocial function during the prenatal (odds ratio 3.55, p = 0.003) and postpartum periods (T1: odds ratio 2.33, p = 0.004). Insomnia disorder is emerging as an important prenatal factor that may contribute to concurrent and postpartum psychopathology.
Court‐hoarding: Another method of gaming judicial turnover
Authors: Leisure Patrick , Kosař David
Published: March 2024

While a slew of recent scholarship has examined the phenomenon of executive overstay, there is little talk about the more complex and equally vexing phenomena of judicial overstay. This article begins to examine the many layers and complexities of judicial overstay by exploring whether the political branches ever seek to prolong abusively the time in office of loyal judges, and if so, by what mechanisms. Illustrating this is not merely a theoretical practice, we label such a phenomenon court‐hoarding, and consider it a subset of the broader category of judicial overstay. Our contribution is two‐fold. First, we argue that while court‐hoarding is a somewhat risky and less‐known governance tactic that is likely to occur only when certain conditions are fulfilled, the potential benefits of court‐hoarding for power consolidation and institutional monopoly power are profound. Second, we contribute to the emerging literature on judicial tenure. More specifically, we add conceptual utility to thinking about judicial tenure—and its abuse—by describing a three‐layer model of court‐hoarding, consisting of a core, a mid‐layer, and a periphery, which correspond to three broad categories of influencing judicial tenure across time and space.
Impact of demographic factors, comorbidities, and co‐medication on progression and survival in a large Chinese ALS cohort
Authors: Hu Nan , Zhang Lei , Shen Dongchao , Yang Xunzhe , Liu Mingsheng , Cui Liying
Published: March 2024

Objective

To clarify the impact of specific risk/protective factors on the disease progression and survival in a large population of Chinese sporadic ALS (sALS) patients.

Methods

We investigated a cohort of 937 sALS patients prospectively. Uni‐ and multivariate regression analysis were performed to analyze the influence of demographic factors, comorbidities and medication on the progression and survival of ALS.

Results

Our results showed younger age of onset (p < 0.05), long diagnostic delay (p < 0.001) and intake of riluzole (p < 0.001) were significantly related to low progression rate and long survival time. History of smoking (p < 0.05) and bulbar onset (p < 0.001) were risk factors for rapid progression and poor prognosis. Baseline ALSFRS‐R score (p < 0.001) and total MRC score (p < 0.05) were positively related to mean survival time of included patients. Neither comorbidities nor intake of antihypertensive drugs, antidiabetics, and statins as dependent variables showed considerable influence on ALS progression or survival.

Conclusion

Our study revealed early onset and long diagnostic delay were indicators of slow progression and long survival. Smoking and bulbar onset were risk factors for shorter survival times and abstaining from smoking was beneficial to patients with ALS in improving median survival time. Long‐term intake of riluzole should be recommended for affordable patients.
Cryoballoon pulmonary vein isolation versus radiofrequency ablation of the pulmonary veins and left atrial posterior wall: Patient‐reported outcomes
Authors: Farwati Medhat , Braghieri Lorenzo , Abdulhai Farah A. , Dabbagh Marwan , Alkhalaileh Firas A. , Younis Arwa , Tabaja Chadi , Farwati Amr , Amin Mustapha , Santangeli Pasquale , Nakagawa Hiroshi , Saliba Walid I. , Kanj Mohamed , Callahan Thomas D. , Bhargava Mandeep , Baranowski Bryan , Rickard John , Sroubek Jakub , Lee Justin , Tchou Patrick J. , Wazni Oussama M. , Hussein Ayman A.
Published: March 2024

Background

Data are lacking on patient‐reported outcomes (PRO) following cryoballoon ablation (CBA) versus radiofrequency ablation (RFA). We sought to evaluate QoL and clinical outcomes of cryoballoon pulmonary vein isolation only (CRYO‐PVI‐ONLY) versus RFA with PVI and posterior wall isolation (RF‐PVI+PWI) in a large prospective PRO registry.

Methods

Patients who underwent AF ablation (2013–2016) at our institution were enrolled in an automated, prospectively maintained PRO registry. CRYO‐PVI‐ONLY patients were matched (1:1) with RF‐PVI+PWI patients based on age, gender, and type of AF (paroxysmal vs. persistent). QoL and clinical outcomes were assessed using PRO surveys at baseline and at 1‐year. The atrial fibrillation symptom severity scale (AFSSS) was the measure for QoL. Additionally, we assessed patient‐reported clinical improvement, arrhythmia recurrence, and AF burden (as indicated by AF frequency and duration scores).

Results

A total of 296 patients were included (148 in each group, 72% paroxysmal). By PRO, a significant improvement in QoL was observed in the overall study population and was comparable between CRYO‐PVI‐ONLY and RF‐PVI+PWI (baseline median AFSSS of 11.5 and 11; reduced to 2 and 4 at 1 year, respectively; p = 0.44). Similarly, the proportion of patients who reported improvement in their overall QoL and AF related symptoms was high and similar between the study groups [92% (CRYO‐PVI‐ONLY) vs. 92.8% (RF‐PVI+PWI); p = 0.88]. Arrhythmia recurrence was significantly more common in the CRYO‐PVI‐ONLY group (39.7%) compared to RF‐PVI+PWI (27.7 %); p = 0.03. Comparable results were observed in paroxysmal and persistent AF.

Conclusion

CRYO‐PVI‐ONLY and RF‐PVI+PWI resulted in comparable improvements in patient reported outcomes including QoL and AF burden; with RF‐PVI+PWI being more effective at reducing recurrences.
Iatrogenic vertebral artery injury during catheter ablation treated using coil embolization
Authors: Oshima Tsukasa , Yamagata Kenichiro , Shimizu Yu , Koizumi Satoshi , Fujiu Katsuhito , Komuro Issei
Published: March 2024

The internal jugular vein (IJV) is occasionally used for blood access during catheter ablation. Additionally, accidental injury of the vertebral artery during an IJV puncture is a rare complication that can result in catastrophic events, such as death. However, vascular access complications cannot be completely prevented despite the introduction of ultrasound‐guided punctures. Here, we present a case of a patient with symptomatic paroxysmal atrial fibrillation that required catheter ablation.
Addressing diversity, equity, and inclusion: A response of professional nursing organizations to the future of nursing: 2020–2030 recommendations
Authors: Campbell Lisa A. , Kelly Patricia J. , Kneipp Shawn M.
Published: March 2024

One way in which professional nursing organizations have chosen to address the social determinants of health (SDoH) is through policy work focused on diversity, health equity and anti‐racism activities. The recent report, Future of Nursing 2020–2030: Charting a Path to Achieve Health Equity (FON 2020–2030), calls on professional nursing organizations and/or nursing coalitions to focus on addressing the SDoH to mitigate health inequities, including a focus on addressing racism and promoting practices to ensure the diversity of the nursing workforce. While these recommendations highlight issues of high importance to nursing and the broader society, they assume that professional nursing organizations or coalitions have not been sufficiently engaged in this work to date. Our goal was to better understand the current and/or ongoing activities of professional nursing organizations around their anti‐racism work of diversity, health equity, and inclusion (DEI) activities recommended in the FON 2020–2030 report. To address this goal, we conducted a needs assessment of professional nursing organizations to document their DEI activities and the timing of these activities relevant to the recommendations in the report. The 26 responding organizations indicated they had been engaged in work addressing DEI issues for periods ranging from 4 months to 51 years. Minimal funding was the major barrier to advancing this work. Creating a vigorous shared DEI agenda across the profession, as suggested in the FON 2020–2030 report, will require input from nurses across the profession, as well as identification of resources to support this critical endeavor.
The business of oyster restoration: using traditional market‐based approaches to estimate the oyster restoration economy
Authors: Hall Elliot , DeAngelis Bryan M.
Published: March 2024

In the United States, restoring oyster reefs is increasingly a priority, due to a desire to return the economic, ecological, and social services the habitat can provide. This growing demand for oyster reef restoration has led to the development of an oyster reef restoration economy. This study was the first to assess it as such, by using similar approaches to private sector market studies. Here, we conducted a market assessment to: quantify the market size in terms of annual dollars spent on oyster reef restoration projects; understand the variation in industry members involved, and market variation by region and state; analyze the distribution of the total market size across the value chain; and document primary factors that will contribute to future market growth or decline. We also used the direct annual spend to estimate the industry's impact on jobs, indirect output, and induced output from the oyster restoration industry on the U.S. economy. In the United States, the oyster reef restoration industry's overall size, measured as annual spend, is $70–90 M, directly supporting an estimated 1500 jobs and contributing $210 M of economic output. Most of the market is directed toward projects whose intended direct result is increased oyster populations versus planning, surveys, or monitoring. The vast majority (85%) of the market resides in the mid‐Atlantic and the Gulf of Mexico regions. Practitioners nearly unanimously agree that the oyster reef restoration industry will continue to grow over the next 5 years.
The integration of GIS location‐based APIs and urban growth modeling for improved geographic access to hospital services
Authors: Sejati Anang Wahyu , Putri Savira Nur Afifah Kusuma , Buchori Imam , de Vries Walter Timo , Barbarossa Ghiffari , Margarena Candra , Bramiana Chely Novia
Published: March 2024

This article aims to present an integration model of GIS with open data sourced from application programming interface (API) as a solution for the location set covering problem (LSCP) with an urban land dynamics model. The development of GIS which is increasingly advanced makes traditional GIS transition in the open data era to become more modern. One of the benefits is to help urban planners in determining the allocation of health facilities such as hospitals. This research takes the case of hospital service coverage during emergencies, especially during the COVID‐19 extraordinary event in Metropolitan Semarang, Indonesia. In addition to utilizing API‐base Location, the model process also uses a Cellular Automata‐based land use prediction model. Thus, the facility location plan not only considers service coverage but also land use growth which is a reflection of population growth. To analyze the problem of inequity of hospital services, this research combined the location‐based APIs‐based service area model with the urban growth model to evaluate the existing condition and predict the future of hospital service demand. It also uses the emergency standard with a maximum service distance of 1500 m and a maximum travel time of 7 min. The model confirmed that there are still critical spots not served by hospitals in Semarang City. According to the concept of health and place, it is essential to recommend adding two hospitals in unserved areas so that services are more evenly distributed in the future, especially in emergencies.
Loss of daylength sensitivity by splice site mutation in Cannabis pseudo‐response regulator
Authors: Leckie Keegan M. , Sawler Jason , Kapos Paul , MacKenzie John O. , Giles Ingrid , Baynes Katherine , Lo Jessica , Baute Gregory J. , Celedon Jose M.
Published: March 2024

Photoperiod insensitivity (auto‐flowering) in drug‐type Cannabis sativa circumvents the need for short day (SD) flowering requirements making outdoor cultivation in high latitudes possible. However, the benefits of photoperiod insensitivity are counterbalanced by low cannabinoid content and poor flower quality in auto‐flowering genotypes. Despite recent studies in cannabis flowering, a mechanistic understanding of photoperiod insensitivity is still lacking. We used a combination of genome‐wide association study and genetic fine‐mapping to identify the genetic cause of auto‐flowering in cannabis. We then used gene expression analyses and transient transformation assays to characterize flowering time control. Herein, we identify a splice site mutation within circadian clock gene PSEUDO‐RESPONSE REGULATOR 37 (CsPRR37) in auto‐flowering cannabis. We show that CsPRR37 represses FT expression and its circadian oscillations transition to a less repressive state during SD as compared to long days (LD). We identify several key circadian clock genes whose expression is altered in auto‐flowering cannabis, particularly under non‐inductive LD. Research into the pervasiveness of this mutation and others affecting flowering time will help elucidate cannabis domestication history and advance cannabis breeding toward a more sustainable outdoor cultivation system.
HSP70A promotes the photosynthetic activity of marine diatom Phaeodactylum tricornutum under high temperature
Authors: Yang Wenting , Gao Shan , Bao Mengjiao , Li Xin , Liu Zhiyuan , Wang Guangce
Published: March 2024

With global climate change, the high‐temperature environment has severely impacted the community structure and phenotype of marine diatoms. Phaeodactylum tricornutum, a model species of marine diatom, is sensitive to high temperature, which grow slowly under high temperature. However, the regulatory mechanism of P. tricornutum in response to high‐temperature is still unclear. In this study, we found that the expression level of the HSP70A in the wild type (WT) increased 28 times when exposed to high temperature (26°C) for 1 h, indicating that HSP70A plays a role in high temperature in P. tricornutum. Furthermore, overexpression and interference of HSP70A have great impact on the exponential growth phase of P. tricornutum under 26°C. Moreover, the results of Co‐immunoprecipitation (Co‐IP) suggested that HSP70A potentially involved in the correct folding of the photosynthetic system‐related proteins (D1/D2), preventing aggregation. The photosynthetic activity results demonstrated that overexpression of HSP70A improves non‐photochemical quenching (NPQ) activity under high‐temperature stress. These results reveal that HSP70A regulates the photosynthetic activity of P. tricornutum under high temperatures. This study not only helps us to understand the photosynthetic activity of marine diatoms to high temperature but also provides a molecular mechanism for HSP70A in P. tricornutum under high‐temperature stress.
Determining the impact of current Canadian stem cell registry policy on donor availability via dynamic registry simulation
Authors: Blake John T. , Ganz Kathy , Seftel Matthew , Allan David
Published: March 2024

Background and Objectives

When a haematopoietic stem cell registry size is constrained by limits on recruiting, as in Canada, identifying the right person to recruit is a critical determinant of effectiveness. The aim of this study was to evaluate the impact of changes to donor recruitment effort, within ethnic groups, on the matching effectiveness of the Canadian registry as it evolves over time.

Materials and Methods

Simulation methods are applied to create a cohort of donor recruits and patients over a 10‐year time horizon. New recruits are added to the registry each year, while some existing donors ‘age‐out’ upon reaching their 36th birthday. In a similar fashion, simulated patient lists are created. At the end of each simulated year, simulated patients are matched against the simulated registry.

Results

There are increased matches in non‐White populations when diverse registrants are preferentially recruited, but there are larger decreases in the number of matches for Caucasian patients. Additionally, ethnic communities that have limited registrants in the Canadian registry in 2021 do not benefit from increased recruiting efforts as much as communities with a larger initial number of registrants.

Conclusion

Preferentially recruiting from non‐Caucasian populations reduces the number of matches from Canadian sources because increases in non‐Caucasian populations will not fully counterbalance decreases to Caucasian patient matches. Nevertheless, more than 80% of all matches are for Caucasian patients, regardless of the donor recruiting effort within ethnic groups.
Long‐term outcome of permanent tracheostomy management in two brachycephalic dogs using a commercial and a three‐dimensional‐printed silicone stent
Authors: Janssen Janina N. , Gradner Gabriele M. , Liehmann Lea
Published: March 2024

Objective

To report the long‐term outcome of utilization of a silicone stent to support the management of a permanent tracheostomy.

Study design

Short case series.

Animals

Two client‐owned brachycephalic dogs.

Methods

Two brachycephalic dogs with stage III laryngeal collapse underwent permanent tracheostomy. After the tracheostomy had healed, a silicone stent was inserted to support the stoma and facilitate home care. One dog wore a commercially available silicone stent for the follow‐up period of 2 years. For the dog in Case 2, a 3D‐printed, medical‐grade silicone stent with an increased length was designed, as the dog had developed skin sores from the commercial device.

Results

Both dogs tolerated the silicone stent well. Stent care was managed by the owners without need for assistance. They reported that the silicone stent facilitated cleaning of the stoma surroundings and that they felt an increased confidence in airway patency, as the device prevented the tracheal stoma from collapsing. In Case 1, tracheoscopy 1 year after first stent insertion revealed minimal visible changes to the tracheal stoma. In Case 2, the 3D printed silicone stent led to a remission of skin sores and the dog wore the device comfortably until succumbing to an unrelated disease 13 months later.

Conclusion

The insertion of a silicone stent is a simple and cost‐effective method to improve home care of dogs with permanent tracheostomy. Larger dogs, as in Case 2, may benefit from custom‐designed 3D‐printed stents.
Process optimization and character evaluation of Bletilla striata polysaccharide (BSP) and chitosan (CS) composite hemostatic sponge (BSP–CS)
Authors: Zhang Yeshan , Han Xue , Zhao Jun , Gan Menglan , Chen Yaya , Zhang Jinxia , He Yu , Wu Mingkai , Liu Hai
Published: March 2024

Bletilla striata polysaccharide (BSP) and chitosan (CS) were chemically cross-linked using oxalyl chloride to prepare a composite hemostatic sponge (BSP-CS), and the process parameters were optimized using the Box–Behnken design (BBD) with response surface methodology. To optimize the performance of the hemostatic sponge, we adjusted the ratio of independent variables, the amount of oxalyl chloride added, and the freeze-dried volume. A series of evaluations were conducted on the hemostatic applicability of BSP-CS. The characterization results revealed that BSP-CS had a stable bacteriostatic effect on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa within 72 h, and the bacteriostatic rate was above 30%. The CCK-8 cytotoxicity test demonstrated that BSP–CS had a certain effect on promoting cell proliferation of L929 cells. In the mouse tail-cutting experiment, the hemostasis time of BSP–CS was 463.0±38.16 s, shortened by 91.3 s on average compared with 554.3±34.67 s of the gauze group. The blood loss of the BSP–CS group was 28.47±3.74 mg, which was 34.7% lower than that of the control gauze group (43.6±3.83 mg). In the in vitro coagulation experiment, the in vitro coagulation index of the BSP–CS group was 97.29%±1.8%, which was reduced to 8.6% of the control group. The CT value of the BSP–CS group was 240±15 s, which was 155 s lower than that of the gauze group (355±31.22 s). All characterization results indicate that BSP–CS is an excellent hemostatic material.
Outcomes by
Candida
spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis
Authors: Locke Jeffrey B. , Pillar Chris M. , Castanheira Mariana , Carvalhaes Cecilia G. , Andes David , Aram Jalal A. , Andrzejewski Christina , Bartizal Ken , Das Anita F. , Sandison Taylor , Thompson George R. , Pappas Peter G.
Published: March 2024

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline
Candida
species is described. Susceptibility testing was performed for
Candida
species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline
Candida
species distribution was similar in the two treatment groups;
C. albicans
(occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively),
C. glabrata
(25.8% and 26.6%), and
C. tropicalis
(21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by
Candida
species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of
Candida
species.
First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus
Authors: Zhou Xiao-Jian , Lickliter Jason , Montrond Maureen , Ishak Laura , Pietropaolo Keith , James Dayle , Belanger Bruce , Horga Arantxa , Hammond Janet
Published: March 2024

AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID). No serious adverse events occurred, and the majority of treatment-emergent adverse events were mild in severity and resolved by the end of the study. In those receiving single ascending doses of AT-752, no pharmacokinetic sensitivity was observed in Asian subjects, and no food effect was observed. Plasma exposure of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, increased with increasing dose levels of AT-752 and exhibited a long half-life of approximately 15–25 h. Administration of AT-752 750 mg TID led to a rapid increase in plasma levels of AT-273 exceeding the target
in vitro
90% effective concentration (EC
90
) of 0.64 µM in inhibiting DENV replication, and maintained this level over the treatment period. The favorable safety and pharmacokinetic results support the evaluation of AT-752 as an antiviral for the treatment of dengue in future clinical studies.

Registered at ClinicalTrials.gov (
NCT04722627
).