bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis
Authors: Marañón Patricia , Isaza Stephania C. , Fernández-García Carlos Ernesto , Rey Esther , Gallego-Durán Rocío , Montero-Vallejo Rocío , de Cía Javier Rodríguez , Ampuero Javier , Valverde Ángela M. , Romero-Gómez Manuel , García-Monzón Carmelo , González-Rodríguez Águeda
Published: April 2023

Background & Aims

Advanced hepatic fibrosis is the main risk factor of liver-related morbidity and mortality in patients with chronic liver disease. In this study, we assessed the potential role of bone morphogenetic protein 8A (BMP8A) as a novel target involved in liver fibrosis progression.

Methods

Histological assessment and BMP8A expression were determined in different murine models of hepatic fibrosis. Furthermore, serum BMP8A was measured in mice with bile duct ligation (BDL), in 36 subjects with histologically normal liver (NL) and in 85 patients with biopsy-proven non-alcoholic steatohepatitis (NASH): 52 with non- or mild fibrosis (F0-F2) and 33 with advanced fibrosis (F3-F4). BMP8A expression and secretion was also determined in cultured human hepatocyte-derived (Huh7) and human hepatic stellate (LX2) cells stimulated with transforming growth factor ꞵ (TGFꞵ).

Results

Bmp8a mRNA levels were significantly upregulated in livers from fibrotic mice compared to control animals. Notably, serum BMP8A levels were also elevated in BDL mice. In addition, in vitro experiments showed increased expression and secretion to the culture supernatant of BMP8A in both Huh7 and LX2 cells treated with TGFꞵ. Noteworthy, we found that serum BMP8A levels were significantly higher in NASH patients with advanced fibrosis than in those with non- or mild fibrosis. In fact, the AUROC of circulating BMP8A concentrations to identify patients with advanced fibrosis (F3-F4) was 0.74 (p˂0.0001). Moreover, we developed an algorithm based on serum BMP8A levels that showed an AUROC of 0.818 (p˂0.0001) to predict advanced fibrosis in NASH patients.

Conclusion

This study provides experimental and clinical evidence indicating that BMP8A is a novel molecular target linked to liver fibrosis and introduces an efficient algorithm based on serum BMP8A levels to screen patients at risk for advanced hepatic fibrosis.
A comprehensive assessment method for the health status of bronzes unearthed at archaeological sites
Authors: Li Juan , Li Li , Xie Zhenbin , Xiang Jiankai , Zhao Xichen , Xiao Qing , Ling Xue
Published: April 2023

As one of the common physical materials in Chinese archaeological excavations, ancient bronzes are an essential basis for studying the development of Chinese bronze culture, which is of great significance for exploring the development law of ancient human civilization and reconstructing ancient human society. As China’s infrastructure advances, the number of bronzes unearthed by archaeological excavations continues to increase. However, environmental damage to artefacts is very complex, whether the buried environment of the artefacts or the above-ground environment when the artefacts are unearthed, leading to different health problems for the excavated bronzes. A scientific assessment of these bronzes needs to be carried out prior to extraction to inform staff how they should be extracted, moved, and transported and how they should be restored afterwards. In response to the above problems, this paper takes excavated bronzes from archaeological sites as the research object and, by analysing and studying the relevant industry standards and the disease characteristics of bronzes, establishes a three-tier indicator framework for assessing the health of bronzes in a layer-by-layer refinement and proposes quantitative indicators with typical correlations. Through extensive research and testing, we screened out efficient, non-destructive, convenient and reliable assessment and testing methods and assessment models that combine subjective and objective aspects suitable for archaeological sites. On this basis, the paper achieves a scientific and practical assessment of the health status of bronzes excavated from archaeological sites. After repeated experiments, a set of comprehensive methods for quickly and conveniently assessing the health status of excavated bronzes was proposed for the first time and successfully applied to the archaeological excavation site of Sanxingdui site in Guanghan City, Sichuan Province, China.
Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine
Authors: Lopes Daniela , Lopes Joana , Pereira-Silva Miguel , Peixoto Diana , Rabiee Navid , Veiga Francisco , Moradi Omid , Guo Zhan-Hu , Wang Xiang-Dong , Conde João , Makvandi Pooyan , Paiva-Santos Ana Cláudia
Published: April 2023

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.
Evaluating an emotion coaching programme for parents of young adolescents attending Child Adolescent Mental Health Services (CAMHS) in New Zealand: protocol for a multi-site feasibility trial including co-design with service users
Authors: Mansoor Zara , Stanley James , Fortune Sarah , Havighurst Sophie , Bell Elliot
Published: April 2023

Background

Early adolescence is a time of increased vulnerability for the development of common mental health conditions such as anxiety and depression (internalising outcomes). Current treatments such as cognitive-behavioural therapy and antidepressant medication are focused on the individual and have small effect sizes, particularly in real-world clinical settings such as the public Child Adolescent Mental Health Services (CAMHS). Parents are an important and under-utilised resource in treating these conditions in young adolescents. Teaching parents how to respond to their young person’s emotions can improve emotion regulation and reduce internalising outcomes. One emotion-focused programme for parents of this age group is Tuning in to Teens (TINT). This is a structured, manualised skills group for parents only focused on teaching skills to coach young people through their emotional experiences. This study aims to investigate the impact of TINT in the clinical setting of publicly funded CAMHS in New Zealand.

Methods

The trial will evaluate the feasibility of a two-arm multi-site randomised control trial (RCT). Participants will be 10–14-year-olds referred to CAMHS in Wellington, New Zealand, with anxiety or depression, and their parents or guardians. Arm 1 will be parents attending and implementing TINT (in addition to the usual care received at CAMHS). Arm 2 will be usual care only. TINT groups will be facilitated by CAMHS clinicians who have been trained in the programme and will be delivered over 8 weekly sessions. Prior to the RCT, a co-design methodology will be used with service users to inform outcome measures used in the trial. A group of service users meeting the RCT criteria will be recruited to take part in workshops to help determine their priority outcomes. Measures based on the results of workshops will be included in the outcome measures. The primary feasibility outcomes will be the recruitment and retention of participants, acceptability of the intervention for service users and clinicians and acceptability of outcome measures.

Discussion

There is a need to improve outcomes for the treatment of adolescent anxiety and depression. TINT is a programme with the potential to enhance outcomes for those accessing mental health services by providing targeted support to parents of adolescents. This trial will inform whether a full RCT is feasible to evaluate TINT. Including service users in the design will increase its relevance of an evaluation in this setting.

Trial registration

The Australian New Zealand Clinical Trials Registry (ACTRN): ACTRN12622000483752. Registered on 28 March 2022.
Adherence therapy for adults with type 2 diabetes: a feasibility study of a randomized controlled trial
Authors: Alenazi Fatimah , Peddle Monica , Bressington Daniel , Mahzari Moeber , Gray Richard
Published: April 2023

Background

Adherence Therapy is a candidate intervention to promote consistent medication taking in people with type 2 diabetes. The aim of this study was to establish the feasibility of conducting a randomized controlled trial of adherence therapy in people with type 2 diabetes who were non-adherent with medication.

Methods

The design is an open-label, single-center, randomized controlled feasibility trial. Participants were randomly allocated to receive either eight sessions of telephone-delivered adherence therapy or treatment as usual. Recruitment occurred during the COVID-19 pandemic. Outcome measures—adherence, beliefs about medication, and average blood glucose (sugar) levels (HbA1c)—were administered at baseline and after 8 weeks (TAU group) or at the completion of the treatment (AT group). Feasibility outcomes included the number of people approached to participate in the trial and the numbers that consented, completed study measures, finished treatment with adherence therapy, and dropped out of the trial. Fieldwork for this trial was conducted in the National Guard Hospital, a tertiary care provider, in the Kingdom of Saudi Arabia.

Results

Seventy-eight people were screened, of which 47 met eligibility criteria and were invited to take part in the trial. Thirty-four people were excluded for various reasons. The remaining thirteen who consented to participate were enrolled in the trial and were randomized (AT,n = 7) (TAU,n = 6). Five (71%) of the seven participants in the adherence therapy arm completed treatment. Baseline measures were completed by all participants. Week 8 (post-treatment) measures were completed by eight (62%) participants. Dropout may have been linked to a poor understanding of what was involved in taking part in the trial.

Conclusions

It may be feasible to conduct a full RCT of adherence therapy, but careful consideration should be given to developing effective recruitment strategies, consent procedures, rigorous field testing, and clear support materials.

Trial registration

The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12619000827134, on the 7th of June 2019.
Review on kidney diseases: types, treatment and potential of stem cell therapy
Authors: Singh Jaspreet , Singh Sanjeev
Published: April 2023

Renal disorders are an emerging global public health issue with a higher growth rate despite progress in supportive therapies. In order to find more promising treatments to stimulate renal repair, stem cell-based technology has been proposed as a potentially therapeutic option. The self-renewal and proliferative nature of stem cells raised the hope to fight against various diseases. Similarly, it opens a new path for the treatment and repair of damaged renal cells. This review focuses on the types of renal diseases; acute and chronic kidney disease—their statistical data, and the conventional drugs used for treatment. It includes the possible stem cell therapy mechanisms involved and outcomes recorded so far, the limitations of using these regenerative medicines, and the progressive improvement in stem cell therapy by adopting approaches like PiggyBac, Sleeping Beauty, and the Sendai virus. Specifically, about the paracrine activities of amniotic fluid stem cells, renal stem cells, embryonic stem cells, mesenchymal stem cell, induced pluripotent stem cells as well as other stem cells.
How does the age of the youngest child affect parental survival?
Authors: Drefahl Sven , Mussino Eleonora
Published: April 2023

Previous research has investigated several different aspects of the relationship between having a child and parental mortality. One aspect of research that has been neglected until now is the age of the child. If children have an effect on parental mortality, this is likely to change as they grow up. We apply hazard regression models to longitudinal Swedish register data of the total population for men and women separately. Adjusting for a variety of control variables, we find that parents with younger children experience a substantive mortality advantage compared to parents—of the same age—who have older children. The mortality advantage decreases gradually as the age of the youngest child increases. Robustness checks confirm that this result cannot be explained by differences in the parent’s age and parental age at first birth. Childless women and men of the same age experience the highest mortality. Additional models for different causes of death suggest that selection, behavioral changes, and unobserved protective effects contribute to this pattern.
Extreme wildfire supersedes long-term fuel treatment influences on fuel and vegetation in chaparral ecosystems of northern California, USA
Authors: Jones Abigail M. , Kane Jeffrey M. , Engber Eamon A. , Martorano Caroline A. , Gibson Jennifer
Published: April 2023

Background

Within California’s chaparral ecosystems, fuel reduction treatments are commonly used to reduce the negative impacts of wildfire but the durability of fuel treatment changes to fuels and vegetation when exposed to wildfire is less well understood. This study examined the interactive effects of 15-year-old fuel treatments and an extreme wildfire on burn severity, fuel loading, and vegetation in chaparral and oak vegetation types in Whiskeytown National Recreation Area in northern California, USA. Fuel treatment types included hand thinned, mechanical mastication, mechanical mastication + prescribed burning, and prescribed burning only.

Results

Vegetation and substrate burn severity was characterized as moderate across the study site and did not differ among treatments. Contrasting with higher pre-fire shrub density in the mastication + burning treatment, 2-year post-fire live shrub density did not differ among treatments. Higher pre-fire fine woody fuel loading in the mastication treatment did not correspond to post-fire fuel loading among treatments, while the hand thinned treatment was the only treatment where fine fuel loading was not significantly reduced post-fire. Total plant species richness increased in all treatment types following wildfire, largely driven by an increase in exotic species. Native cover decreased, and exotic cover increased in oak and chaparral types, but greater exotic species cover in the mastication + burning treatment in chaparral was maintained following wildfire.

Conclusions

Pre-fire differences in fuel and vegetation responses among treatments largely did not persist or were not detectible 1 to 2 years following wildfire. These findings suggest that the extreme wildfire conditions superseded long-term treatment differences in many fuel and vegetation metrics observed prior to wildfire. Despite subtle treatment differences, the hand thinned treatment resulted in the lowest change in fuel loading relative to all other treatments. Lastly, pre-fire differences in exotic species among fuel treatments were retained following wildfire, suggesting some treatments may have greater potential for exotic species expansion or type conversion to exotic grasslands.
Medial patellofemoral ligament reconstruction and tibial tuberosity transfer can be used to successfully manage patellofemoral instability in the setting of trochlea dysplasia
Authors: Dewan Varun , Gudipati Suribabu , Rooney Joanna , Lloyd Adam , Chugh Sanjiv , Mughal Ejaz
Published: April 2023

Background

Management of patella instability remains a challenge particularly in the presence of trochlea dysplasia. The aim of this study is to assess the recurrence rates of those with patellar instability who have undergone a combined tibial tuberosity transfer (TTT) and medial patellofemoral ligament reconstruction (MPFLR) in the setting of trochlea dysplasia.

Methods

All skeletally mature patients who underwent combined TTT and MPFLR for recurrent patella instability were identified between January 2009 and December 2019. A retrospective review was conducted, with information regarding re-dislocation/subluxation and complications collected.

Results

Seventy patients with a mean age 25.3 years were identified and evaluated. Thirteen patients were found to have low-grade dysplasia (Dejour A), with 57 patients having high-grade dysplasia (Dejour B/C/D). No patients in the low,grade dysplasia group suffered a recurrence of their symptoms, with four in the high-grade group suffering episodes of re-dislocation/subluxation. Three patients subsequently underwent a trochleoplasty, with the other patient managed successfully non-operatively. There were a total of 13 complications in 11 patients.

Conclusions

A combined procedure of MPFLR and TTT can be used to manage patellofemoral instability even in the setting of trochlea dysplasia with a low rate of recurrence. Trochlea dysplasia, however, remains an anatomical risk factor for recurrence and patients should be counselled accordingly. The anatomical risk factors should be assessed in all patients to allow for the development of the most appropriate management plan, of which this combined procedure represents a potentially successful option.

Level of Evidence

IV (Case Series).
Assessment of symptoms of the post-COVID-19 syndrome in patients with different rheumatic diseases
Authors: Ismail Zahraa Nour Eldine , Hefny Mohamed Ahmed , Hendi Ahmed Elarabi , Tawfik Marwa Gamal
Published: April 2023

Background

Patients with rheumatic diseases significantly suffer during and after infection with coronavirus disease (COVID-19). Post-COVID-19 syndrome (PCS) refers to signs and symptoms occurring during or following a COVID-19 infection that continue beyond 12 weeks. The study aimed to assess PCS symptoms in rheumatic disease patients compared to a control group not suffering from a rheumatic disease or any other chronic illness.

Results

The prevalence of PCS symptoms was significantly higher in rheumatic disease patients compared to the control group: fatigue (69.1% vs. 41.25%), myalgia (73.5% vs. 37.5%), attention deficits (57.4% vs. 40%), and muscle weakness (33.8% vs. 13.8%). Objectively, the study group had significantly higher scores for the Fatigue Severity Scale (FSS) (35.46 ± 13.146 vs. 25.1 ± 7.587), Short-form McGill Pain Questionnaire (SF-MPQ-2) (21.66 ± 10.3 vs. 11.6 ± 3.433), and higher grades of functional disability in the Post-COVID-19 Functional Status scale (PCFS). Rheumatic disease patients had significantly higher frequencies of anxiety and depression, as assessed by the Hospital Anxiety and Depression Scale (HADS), and cognitive impairment, as assessed by the Mini-Mental State Examination (MMSE), than the controls (P = 0.023,P = 0.003,P = 0.0001, respectively). Moreover, SLE patients had the most symptoms and the highest FSS, SF-MPQ-2, PCFS, and HADS scores, as well as the lowest MMSE scores (P = 0.0001 for all except cough (P = 0.043), weakness (P = 0.015), paresthesia (P = 0.027), and anosmia (P = 0.039)). Lower disease duration, hospitalization during acute COVID-19, steroid use, smoking, and biologics non-use were significantly associated with higher PCS symptoms. Smoking was a significant risk factor (P = 0.048), and biologics use was protective (P = 0.03). Rheumatic disease patients who received two doses of the COVID-19 vaccinations had better scores on the FSS, HADS for anxiety and depression, and MMSE than those who received a single dose (P = 0.005,P = 0.001,P = 0.009,P = 0.01).

Conclusion

Rheumatic disease patients have a higher prevalence and risk of PCS, so strict follow-up, avoiding smoking, controlling disease activity, and COVID-19 vaccinations are essential for decreasing the morbidity of PCS.
Electric vehicle integration’s impacts on power quality in distribution network and associated mitigation measures: a review
Authors: Srivastava Abhinav , Manas Munish , Dubey Rajesh Kumar
Published: April 2023

The problem of global warming, along with environmental concerns, has already led governments to replace fossil-fuel vehicles with low-emission electric vehicles (EVs). The energy crisis and environmental problems, such as global warming and air pollution, are essential reasons for the development of electric vehicles (EVs). Electric vehicles are one of the most fascinating and essential fields to emerge in recent years. According to the current report, electric vehicles are attempting to replace older, traditional automobiles. These vehicles not only help to reduce pollution but also to save natural resources. The presence of electric vehicles may cause several problems for the conventional electrical grid due to their grid-to-vehicle (G2V) and vehicle-to-grid (V2G) charging and discharging capabilities. With increased EV adoption, many power quality (PQ) issues in the electrical distribution system arise. With the penetration of EVs in distribution networks, power quality issues such as voltage imbalance, transformer failure, and harmonic distortion are expected to arise. The focus of this research is on exploring and reviewing the issues that the integration of EVs poses for electrical networks. The existing and future situations of electric vehicles’ integration, as well as new research on the subjects, have been reviewed in this paper. This study provides a thorough examination of power quality issues and their mitigating approaches.
Adoptive Cell Therapy for Nonhematologic Solid Tumors
Authors: Olson Daniel J. , Odunsi Kunle
Published: April 2023

The long-term benefits demonstrated by immunotherapy in select tumors have failed to generalize to most nonhematologic solid tumors. Adoptive cell therapy (ACT)—a treatment on the basis of the isolation and engineering of living T cells and other immune cells—has shown early clinical advances. ACT, through tumor-infiltrating lymphocyte therapy, has shown activity in traditionally immunogenic tumors such as melanoma and cervical cancers, and has the potential to improve immune reactivity in these tumor types where traditional therapies have failed. Engineered T-cell receptor and chimeric antigen receptor T-cell therapies have also shown activity in select nonhematologic solid tumors. Through receptor engineering, and improved understanding of tumor antigens, these therapies have the potential to target poorly immunogenic tumors to deliver long-lasting responses. Additionally, non–T-cell therapies such as natural killer–cell therapy may allow for allogeneic forms of ACT. Each form of ACT has trade-offs that will likely limit their application to specific clinical settings. Key challenges with ACT include the logistical challenges of manufacturing, accurate antigen identification, and the risk of on-target, off-tumor toxicity. The successes of ACT are built on decades of advances in cancer immunology, antigen identification, and cell engineering. With continued refinements in these processes, ACT may extend the benefits of immunotherapy to more patients with advanced nonhematologic solid tumors. Herein, we review the major forms of ACT, their successes, and strategies to overcome the trade-offs of current ACTs.
A Year at the Forefront of Bacterial Defense Systems Against Neutrophilic Oxidants
Authors: Sultana Sadia , Dahl Jan-Ulrik
Published: April 2023

One challenge for invading pathogens represents the exposure to highly microbicidal hypohalous acids (HOX), such as hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Generated at high concentrations by innate immune cells during phagocytosis, HOX kills the engulfed microbes through extensive macromolecular damage. However, microorganisms have evolved strategies to detoxify the oxidants and/or alleviate HOX-mediated damage, which improves their survival during HOX exposure. Many of these defense systems are bacteria-specific and therefore considered potential drug targets. Our minireview highlights recent (July 2021 to November 2022) advances in the field of microbial HOX defense systems and how these systems are regulated. We report recent progress on redox-sensing transcriptional regulators, two-component systems, and σ/anti-σ factors and review how oxidative modifications in these regulatory proteins affect the expression of their target genes. Moreover, we discuss novel studies that describe how HOCl affects the activity of redox-regulated enzymes and highlight mechanisms that bacteria employ to reduce HOSCN.
Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation
Authors: Goodwin Amanda T. , John Alison E. , Joseph Chitra , Habgood Anthony , Tatler Amanda L. , Susztak Katalin , Palmer Matthew , Offermanns Stefan , Henderson Neil C. , Jenkins R. Gisli
Published: April 2023

Alveolar development and repair require tight spatiotemporal regulation of numerous signalling pathways that are influenced by chemical and mechanical stimuli. Mesenchymal cells play key roles in numerous developmental processes. Transforming growth factor-β (TGFβ) is essential for alveologenesis and lung repair, and the G protein α subunits Gαq and Gα11 (Gαq/11) transmit mechanical and chemical signals to activate TGFβ in epithelial cells. To understand the role of mesenchymal Gαq/11 in lung development, we generated constitutive (Pdgfrb-Cre+/−;Gnaqfl/fl;Gna11−/−) and inducible (Pdgfrb-Cre/ERT2+/−;Gnaqfl/fl;Gna11−/−) mesenchymal Gαq/11 deleted mice. Mice with constitutive Gαq/11 gene deletion exhibited abnormal alveolar development, with suppressed myofibroblast differentiation, altered mesenchymal cell synthetic function, and reduced lung TGFβ2 deposition, as well as kidney abnormalities. Tamoxifen-induced mesenchymal Gαq/11 gene deletion in adult mice resulted in emphysema associated with reduced TGFβ2 and elastin deposition. Cyclical mechanical stretch-induced TGFβ activation required Gαq/11 signalling and serine protease activity, but was independent of integrins, suggesting an isoform-specific role for TGFβ2 in this model. These data highlight a previously undescribed mechanism of cyclical stretch-induced Gαq/11-dependent TGFβ2 signalling in mesenchymal cells, which is imperative for normal alveologenesis and maintenance of lung homeostasis.
Evidence implicating sequential commitment of the founder lineages in the human blastocyst by order of hypoblast gene activation
Authors: Corujo-Simon Elena , Radley Arthur H. , Nichols Jennifer
Published: April 2023

Successful human pregnancy depends upon rapid establishment of three founder lineages: the trophectoderm, epiblast and hypoblast, which together form the blastocyst. Each plays an essential role in preparing the embryo for implantation and subsequent development. Several models have been proposed to define the lineage segregation. One suggests that all lineages specify simultaneously; another favours the differentiation of the trophectoderm before separation of the epiblast and hypoblast, either via differentiation of the hypoblast from the established epiblast, or production of both tissues from the inner cell mass precursor. To begin to resolve this discrepancy and thereby understand the sequential process for production of viable human embryos, we investigated the expression order of genes associated with emergence of hypoblast. Based upon published data and immunofluorescence analysis for candidate genes, we present a basic blueprint for human hypoblast differentiation, lending support to the proposed model of sequential segregation of the founder lineages of the human blastocyst. The first characterised marker, specific initially to the early inner cell mass, and subsequently identifying presumptive hypoblast, is PDGFRA, followed by SOX17, FOXA2 and GATA4 in sequence as the hypoblast becomes committed.
Nobel Lecture: Banking, Credit, and Economic Fluctuations
Authors: Bernanke Ben S.
Published: April 2023

Credit markets, including the market for bank loans, are characterized by imperfect and asymmetric information. These informational frictions can interact with other economic forces to produce periods of credit-market stress, in which intermediation is unusually costly and households and businesses have difficulty obtaining credit. A high level of credit-market stress, as in a severe financial crisis, may in turn produce a deep and prolonged recession. I present evidence that financial distress and disrupted credit markets were important sources of the Great Depression of the 1930s and the Great Recession of 2007–2009. Changes in the state of credit markets also play a role in “ garden-variety” business cycles and in the transmission of monetary policy to the economy. (JEL D82, E32, E44, E52, G21, N22)
Law and Norms: Empirical Evidence
Authors: Lane Tom , Nosenzo Daniele , Sonderegger Silvia
Published: April 2023

A large theoretical literature argues laws exert a causal effect on norms, but empirical evidence remains scant. Using a novel identification strategy, we provide a compelling empirical test of this proposition. We use incentivized vignette experiments to directly measure social norms relating to actions subject to legal thresholds. Our large-scale experiments (n = 7,000) run in the United Kingdom, United States, and China show that laws can causally influence social norms. Results are robust across different samples and methods of measuring norms, and are consistent with a model of social image concerns where individuals care about the inferences others make about their underlying prosociality. (JEL C91, C92, D91, K00, K42, P37)
Smart Contracts and the Coase Conjecture
Authors: Brzustowski Thomas , Georgiadis-Harris Alkis , Szentes Balázs
Published: April 2023

This paper reconsiders the problem of a durable-good monopolist who cannot make intertemporal commitments. The buyer’s valuation is binary and his private information. The seller has access to dynamic contracts and, in each period, decides whether to deploy the previous period’s contract or to replace it with a new one. The main result of the paper is that the Coase conjecture fails: the monopo-list’s payoff is bounded away from the low valuation irrespective of the discount factor. (JEL D42, D82, D86, L12)
Implementation of AI image reconstruction in CT—how is it validated and what dose reductions can be achieved
Authors: Brady Samuel L
Published: April 2023

CT reconstruction has undergone a substantial change over the last decade with the introduction of iterative reconstruction (IR) and now with deep learning reconstruction (DLR). In this review, DLR will be compared to IR and filtered back-projection (FBP) reconstructions. Comparisons will be made using image quality metrics such as noise power spectrum, contrast-dependent task-based transfer function, and non-prewhitening filter detectability index (dNPW'). Discussion on how DLR has impacted CT image quality, low-contrast detectability, and diagnostic confidence will be provided. DLR has shown the ability to improve in areas that IR is lacking, namely: noise magnitude reduction does not alter noise texture to the degree that IR did, and the noise texture found in DLR is more aligned with noise texture of an FBP reconstruction. Additionally, the dose reduction potential for DLR is shown to be greater than IR. For IR, the consensus was dose reduction should be limited to no more than 15–30% to preserve low-contrast detectability. For DLR, initial phantom and patient observer studies have shown acceptable dose reduction between 44 and 83% for both low- and high-contrast object detectability tasks. Ultimately, DLR is able to be used for CT reconstruction in place of IR, making it an easy “turnkey” upgrade for CT reconstruction. DLR for CT is actively being improved as more vendor options are being developed and current DLR options are being enhanced with second generation algorithms being released. DLR is still in its developmental early stages, but is shown to be a promising future for CT reconstruction.
The first released available genome of the common ice plant (Mesembryanthemum crystallinum L.) extended the research region on salt tolerance, C3-CAM photosynthetic conversion, and halophism
Authors: Sato Ryoma , Kondo Yuri , Agarie Sakae
Published: April 2023

Background: The common ice plant (Mesembryanthemum crystallinum L.) is an annual herb belonging to the genus Mesembryanthemum of the family Aizoaceae, native to Southern Africa.

Methods: We performed shotgun genome paired-end sequencing using the Illumina platform to determine the genome sequence of the ice plants. We assembled the whole genome sequences using the genome assembler “ALGA” and “Redundans”, then released them as available genomic information. Finally, we mainly estimated the potential genomic function by the homology search method.

Results: A draft genome was generated with a total length of 286 Mb corresponding to 79.2% of the estimated genome size (361 Mb), consisting of 49,782 contigs. It encompassed 93.49% of the genes of terrestrial higher plants, 99.5% of the ice plant transcriptome, and 100% of known DNA sequences. In addition, 110.9 Mb (38.8%) of repetitive sequences and untranslated regions, 971 tRNA, and 100 miRNA loci were identified, and their effects on stress tolerance and photosynthesis were investigated. Molecular phylogenetic analysis based on ribosomal DNA among 26 kinds of plant species revealed genetic similarity between the ice plant and poplar, which have salt tolerance. Overall, 35,702 protein-coding regions were identified in the genome, of which 56.05% to 82.59% were annotated and submitted to domain searches and gene ontology (GO) analyses, which found that eighteen GO terms stood out among five plant species. These terms were related to biological defense, growth, reproduction, transcription, post-transcription, and intermembrane transportation, regarded as one of the fundamental results of using the utilized ice plant genome.

Conclusions: The information that we characterized is useful for elucidation of the mechanism of growth promotion under salinity and reversible conversion of the photosynthetic type from C3 to Crassulacean Acid Metabolism (CAM).
Invisibility in global health: A case for disturbing bioethical frameworks
Authors: Alenichev Arsenii , Suwalowska Halina , Faure Marlyn C. , Ng Shu Hui , Modlin Chelsea , Ambrogi Ilana , Parker Michael , Kingori Patricia
Published: April 2023

In recent years, the global health community has been increasingly reporting the problem of ‘invisibility’ as aspects of health and wellbeing that are often overlooked and ignored, and predominantly affects the most marginalized and precarious people. However, it is unclear how to realistically manage global health invisibility and move forward. In this letter, we reflect on several case studies of invisibility experienced by people in Brazil, Malaysia, West Africa and other transnational contexts. Highlighting the complex nature of invisibility and its interconnectedness with social, political and economic issues and trends, we argue that while local and targeted interventions might provide relief and comfort locally, they will not be able to solve the underlying causes of invisibility. Moving forward, we argue that in dealing with an intersectional issue such as invisibility, twenty-first century global health bioethics could pursue a more ‘disturbing’ framework, challenging the narrow comforting solutions and sociomaterial inequalities of the sociopolitical status quo. We highlight that comforting and disturbing bioethical frameworks should not be considered as opposing sides, but as two approaches working in tandem in order to achieve the internationally set global health milestones of providing better health and wellbeing for everyone. In doing so, we call for taking seriously insights from sociology, anthropology, postcolonial studies, history, feminist studies and other styles of critical reasoning that have long been disturbing the grand assumptions about people and their conditions, and, practically, to rediscover the ethos of the WHO Alma Ata Declaration, calling for cooperation and support beyond the narrow market logic that dominates the landscape of contemporary global health.
The genome sequence of the Lesser Broad-bordered Yellow Underwing, Noctua janthe (Borkhausen, 1792)
Authors: Boyes Douglas , Holland Peter W.H. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: April 2023

We present a genome assembly from an individual male Noctua janthe (the Lesser Broad-bordered Yellow Underwing; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 532.8 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 17,653 protein coding genes.
A disfiguring and fatal case of mucormycosis after dexamethasone treatment for a COVID-19 infection
Authors: Guerin Cynthia , Pederson Addie , Chaudhury Tristin , Freedman Kenn , Ray Coby
Published: April 2023

This case report describes a patient with uncontrolled type 2 diabetes mellitus who received steroids for an outpatient infection of COVID-19. The steroid course combined with his acute illness likely contributed to his development of extremely high blood sugar levels (790 mg/dL) and subsequent hyperosmolar hyperglycemic syndrome. In this compromised state, he contracted invasive mucormycosis of the right sinuses and right orbit. This fungal infection caused him to lose his eye and, later, his life. Prescribing systemic steroids comes with many risks. Providers must be careful to use them only when absolutely indicated, especially in patients who are vulnerable to complications, such as those with uncontrolled type 2 diabetes. This case is a grim example of the dangers that can occur with systemic steroid usage.
Milky fluid from where? You are about to find out…
Authors: Peralta Cesar , Ramos Jose
Published: April 2023

Traumatic chylothorax most commonly occurs after thoracic surgeries with a few cases reported in patients after abdominal surgery. Effusions usually are caused by a pleural reaction during the postoperative period. However, this can also occur from disruption of the thoracic duct during the surgical procedure. The initial approach is conservative with supportive measures, including drainage by ultrasound-guided thoracentesis and diet modification, and surgery is rarely needed. Having a medical history preceding abdominal surgery is always important to consider the possibility of a pancreatic pleural fistula, which can be excluded by an abdominal computed tomography. Lymphangiography is considered the gold standard diagnostic tool, but its use is limited to cases unresponsive to conservative measures. In this patient, a lymphangiography or surgical intervention was not performed since the patient improved after initial management with no recurrent pleural effusion. A new pleural effusion after abdominal surgery must include chylothorax in the differential diagnosis.Keywords: Traumatic chylothorax, hiatal hernia repair, thoracic duct, lymphangiography, abdominal computed tomography
Detect Polyphenol and Fatty Acid Content of Two Wild Plants Collected in Mazne Sub-district, Kurdistan Region of Iraq
Authors: Kurdi Samiaa J. Abdulwahid-
Published: April 2023

Celtis tournefortii Lam and Prosopis farcta plant's antioxidant and polyphenolic characteristics have been attributed to the various phytochemicals, including phenolic and fatty acids, present in the crude extract in the leaves, fruits, pods, and seeds. This study's aim is to determine the entire phytochemical compositions of the leaf and fruit reflect Celtis tournefortii Lam, while pod and seed represent Prosopis farcta from Mazne sub-district, including proximate analysis, total antioxidant capacity, total organic acids, ascorbic acids, polyphenols, and fatty acids following established procedures. Pods have higher levels of fiber (41± 0.05 mg/100 g), protein (20.3±0.05%), and vitamin C (26.47±0.03 mg/100 g) from Prosopis farcta, although fruit has higher levels of total antioxidants (89.54± 0.28%) and organic acid (1576±0.57 mg/kg) from Celtis tournefortii Lam. Gallic acid (10.56±0.03 mg/kg) had the highest concentration of polyphenols, whereas the pod contained the highest concentrations of quercetin (11.27±0.14 mg/kg), rutin (13.0±0.57 mg/kg), coumaric acid (2140.57 mg/kg), and chlorogenic acid (659.0±0.57 mg/kg). Oleic acid 32.60±0.24%, Cis-11-Eicosenoic 3.20±0.11%, and Cis-4,7,10,13,16,19-Docosahexaenoic 2.10±0.05% were the most prevalent unsaturated fatty acids in the seed, whereas palmitic 17.40±0.05% and tricosanoic 6.40±0.05% were the most prevalent saturated fatty acids in the leaves. Overall, seeds had the highest concentration of unsaturated fatty acids (74.44%), while leaves had the highest concentration of saturated fatty acids (44.42%). This study identifies two untamed plants, Celtis tournefortii Lam and Prosopis farcta, as potential new sources of natural oil and beneficial natural ingredients.
Vitamin D on COVID-19 Patients During the Pandemic, 2022. A Systematic Review and Meta-Analysis
Authors: Asla Moamen Mostafa , Nawar Asmaa Ahmed , Elsayed Esraa , Farahat Ramadan Abdelmoez , Abdulgadir Ayah , Alsharabasy Mostafa Abdullah , Elshahawy sraa Mohamed , Amer Samar A.
Published: April 2023

Numerous connections between the level of vitamin D (Vit-D) and the novel coronavirus disease -19 (COVID-19) have surfaced during the pandemic. So, we conducted this systematic review and meta-analysis to explore the effect of Vit-D deficiency and its supplementation on the clinical outcomes of COVID-19 patients. We looked for relevant articles in Cochrane Library, Scopus, Web Science, PubMed, and EBSCO up until the end of 2022. The Open Meta Analyst software was used to analyze the extracted data. We classified them into two main categories based on their objectives. First, the studies that evaluated the effects of Vit-D deficiency in patients, and lastly, the studies that evaluated Vit-D as a supplement, both on mortality rate, hospitalization duration, ICU admission rate, and mechanical ventilation rate. A total of 8001 COVID-19 patients from 42 studies were included. A high serum Vit-D concentration compared to those with lower levels was associated with a significantly lower mortality rate (RR = 1.5, 95% CI = 1.11: 2.02, p = 0.01). According to the estimated effect of 18 studies, those who took Vit-D supplements had a significantly lower mortality rate, hospitalization duration, ICU admission rate, and mechanical ventilation rate than those who did not. The group receiving Vit-D doses between 50 000 to 100 000 IU had a significantly better clinical outcome compared to lower and higher doses. COVID-19 patients with normal Vit-D levels had significantly lower death rates than those with hypovitaminosis. Vit-D supplements in COVID-19 significantly improved clinical outcomes. Vit-D supplementation between 50 000 to 100 000 IU, in patients with COVID-19 significantly outperformed other doses in terms of mortality.
Valorization and Chemical Constituents Assessments of Khalas Dates Fruit, Syrup and Pits
Authors: Aleid Salah Mohammed , Haddadin Jamal Saleh
Published: April 2023

This study was conducted to contribute to the national approach to achieving food security in Saudi Arabia, which is one of the world's largest producer of dates. Studying the chemical properties of the most commercial date’s fruits cultivar in the eastern region will contribute to understanding to industrial potential Khalas dates. This is in addition to developing a method for extracting date syrup (DS) in a way that preserves as much nutritional properties as possible. Date fruits (DF) flesh and water mixture at a 1:3 ratio gave 18% total soluble solids (TSS) then concentrated to 70° Brix. The used date flesh to water ratio recaptured all sugars, acetic, butyric and propionic acids in DS. Sugars were the major components amounting 34.3 and 32.6% glucose and fructose, respectively. No crude or dietary fibers were present in DS due to their insolubility in water. In contrast, the major portion of minerals was recovered in DS. In the same way, 60% and 4.9% of the fat and protein respectively were recovered in the DS. It also notes that the main amino acid in DS is glutamic acid which represents 16.25 % of the total detected amino acids. In concentrated DS a total polyphenol (PP) tenor of 1448.65 mg/100 g gallic acid equivalent (GAE) was recovered. The presence of large amounts of PP in DS compared to whole dates can be explained by the use of high temperature DS extraction with vacuum evaporation of excess water.

Crude and dietary fibers were the major components in date pits (DP) representing 24.1% and 56.1% respectively. Fat and sucrose were also present in a significant portion in DP showing 5.9% and 2.4%, respectively. Therefore, the results obtained will serve many food and nutrition industries as well as the pharmaceutical and therapeutic industries.
Initiating end-of-life care
Authors: Farrington Liz , Mortimore Gerri
Published: April 2023

This article will reflect on a case study from practice in which end-of-life care (EOLC) was initiated for a patient, after a period of hesitation. It will explore the possible reasons for this delay, especially in relation to the withdrawal of medical treatment and the role of advanced clinical practitioners in EOLC decision making.
EFL Educators’ Insights into Online Education and its Impact on Teaching during the COVID-19 Pandemic
Authors: Hidalgo-Camacho Cynthia , Villacís Wilma Villacís , Escudero Gloria Isabel , Silva Juan Carlos
Published: April 2023

After months of 100% online teaching due to the pandemic produced by COVID-19, the return to face-to-face classes is being experienced. This study focused on finding the English as a foreign language (EFL) University professors’ perspectives of online education during that time. The information was collected from three Ecuadorian universities: The Technical University of Ambato, The Higher Polytechnic School of Chimborazo, and The University of Cuenca. The survey was designed with 26 questions about professors’ perceptions of online teaching and its impact on their pedagogical practices, affective factors, and student achievement. Software R, and the Cronbach's alpha tests were used as statistical tools, along with Kendall's Tau_b, and the Kruskal-Wallis test. The results showed that teaching online not only represents a solution in cases where face-to-face education is not possible, but also offers teachers the opportunity to experience the benefits of using technological tools and innovative strategies. Although some drawbacks, such as lack of time and real interaction were encountered, online teaching resulted in an alternative methodology that engaged learners.