bluuebunny/crossref_metadata_2025 huggingface dataset:
First characterization of the intestinal microbiota in healthy Tunisian adults using 16S rRNA gene sequencing
Authors: Mahjoub Khachroub Ahlem , Monnoye Magali , Bouhlel Nour Elhouda , Azaiez Sana , Ben Fredj Maha , Mansour Wejdene , Gérard Philippe
Published: June 2023

The gut microbiota is currently recognized as an important factor influencing the host’s metabolism, immune, and central nervous systems. Determination of the composition of the gut microbiota of healthy subjects is therefore necessary to establish a baseline for the detection of alterations in the microbiota under pathological conditions. So far, most studies describing the gut microbiota have been performed in populations from Asia, North America, and Europe, whereas populations from Africa have been overlooked. Here, we present the first characterization of the intestinal microbiota in healthy Tunisian adults using 16S rRNA gene sequencing. We further compare the gut microbiota composition based on gender and BMI. Our results showed that the Tunisian gut microbiota is dominated by the phyla Firmicutes and Bacteroidota in accordance with studies from western countries. However, some specificities have been identified, including a higher proportion of Firmicutes in males and higher proportions of Atopobiaceae and Peptostreptococcaceae in Tunisian overweight individuals. Moreover, we were able to identify bacterial species differently represented between males and females and between normal weight and overweight individuals. These results constitute an important baseline that can be used to identify the dysbiosis associated with the main diseases affecting the Tunisian population.
Digital Prompts and Narrative Cues: Storytelling in the 1450s and in the 2020s
Authors: Emerson Catherine
Published: June 2023

The Cent Nouvelles nouvelles present challenges to student learners of French linguistically, culturally and in terms of the content of the stories. Investigations designed to interrogate how the stories might have been collected in the second half of the fifteenth century end up demonstrating how the storytelling environment shapes the stories that are told and the way that they are understood. The experience of storytelling online during a period of pandemic learning is very different from the same experience in a pre- or post-pandemic classroom. Methodologies, such as critical pedagogy and inquiry stance pedagogy, which had limited resonance in the pre-pandemic environment, became much more central to the learner’s experience in the online, pandemic environment. This confirms the practices of ‘Flux pedagogy’, as advocated by Sharon M. Ravitch. Similarly, reactions to a story featuring the transmission of plague can be shaped by a framing that includes or excludes direct reference to the risk of infection experienced by the listeners.
Relationships Between Adherence to Guideline Recommendations for Pharmacological Therapy Among Clinicians and Psychotic Symptoms in Patients With Schizophrenia
Authors: Kodaka Fumitoshi , Ohi Kazutaka , Yasuda Yuka , Fujimoto Michiko , Yamamori Hidenaga , Hasegawa Naomi , Ito Satsuki , Fukumoto Kentaro , Matsumoto Junya , Miura Kenichiro , Yasui-Furukori Norio , Hashimoto Ryota
Published: June 2023

Background

Clinician adherence to guideline recommendations in the pharmacological therapy of schizophrenia is important for favorable patient outcomes. To evaluate whether prescriptions followed the guidelines for pharmacological therapy of schizophrenia, we recently developed a summary indicator of multiple quality indicators: the individual fitness score (IFS). It is unclear whether adherence to the guidelines is related to patient outcomes. Here, we investigated correlations between the IFS values and psychotic symptoms in patients with schizophrenia.

Methods

We assessed whether patients’ current prescriptions adhered to the guideline recommendations using the IFS in 47 patients with treatment-resistant schizophrenia (TRS) and 353 patients with non-TRS (total n = 400), respectively. We investigated correlations between the IFS and total scores and scores on the 5 subscales of the Positive and Negative Syndrome Scale (PANSS). Furthermore, we explored correlations between over 2-year longitudinal changes in IFS values and changes in psychotic symptoms in some patients (n = 77).

Results

We found significant negative correlation between the IFS and PANSS total score in all patients with schizophrenia (β = −0.18, P = 9.80 × 10−5). The IFS was significantly and nominally negatively correlated with the PANSS total score in patients with non-TRS (Spearman’s rho = −0.15, P = 4.40 × 10−3) and patients with TRS (rho = −0.37, P = .011), respectively. The IFS was also significantly and nominally negatively correlated with several factors, such as the negative and depressed factors, in patients with non-TRS and patients with TRS, respectively (P < .05). Furthermore, the change in IFS values was marginally negatively correlated with the changes in PANSS total scores and scores on the positive and depressed factors (P < .05).

Conclusions

These findings suggest that efforts to improve clinician adherence to guideline recommendations for pharmacological therapy of schizophrenia, as assessed by the IFS, may lead to better outcomes in patients with schizophrenia.
Communication Mediation in an Era of Partisan Selectivity: Modeling Effects of Information and Discussion on Participation
Authors: Lee Seungsu , Cho Jaeho
Published: June 2023

The present study applies the communication mediation model (CMM) to the increasingly prevalent patterns of partisan communication in contemporary polarized politics and fragmented partisan media environments. Specifically, we test the CMM considering (a) two types of news consumption (like-minded and cross-cutting) in the place of overall news use and (b) both affective and cognitive responses. We propose a partisan CMM that consists of a two-step mediation linking partisan news consumption to participation through talk and affective polarization. Results from national survey data covering three U.S. presidential election cycles (the 2012, 2016, and 2020 American National Election Studies) generally supported the model, with like-minded and cross-cutting news use having differential mediation processes on participation.
How Locally Owned and Sustainable Are Victims’ Groups in Postconflict and Transitional Settings? Reflections from Northern Uganda
Authors: Schulz Philipp
Published: June 2023

Victims’ groups in postconflict settings have gained increasing attention in transitional justice scholarship and programming, as entry points for victims to engage with external transitional justice mechanisms, or as vehicles to facilitate healing, recovery or justice making on the micro level. These groups are often presented in terms of local ownership, victims’ participation and self-reliance. Based on work in Uganda, I have previously argued that victims’ groups constitute locally owned and sustainable resources that can facilitate a sense of justice for survivors on their own terms. Yet, based on recent field research observations, I have to ask myself: how locally owned and sustainable are these groups really? Due to a lack of donor support and external resources, the group that I worked with has become inactive since 2020. In this Note, I explore the reasons for and implications of this, with the intention of critically engaging with some of my previous arguments.
Effectiveness of sitafloxacin monotherapy for quinolone-resistant rectal and urogenital Mycoplasma genitalium infections: a prospective cohort study
Authors: Ando Naokatsu , Mizushima Daisuke , Takano Misao , Mitobe Morika , Kobayashi Kai , Kubota Hiroaki , Miyake Hirofumi , Suzuki Jun , Sadamasu Kenji , Aoki Takahiro , Watanabe Koji , Uemura Haruka , Yanagawa Yasuaki , Gatanaga Hiroyuki , Oka Shinichi
Published: June 2023

Background

Mycoplasma genitalium has a tendency to develop macrolide and quinolone resistance.

Objectives

We investigated the microbiological cure rate of a 7 day course of sitafloxacin for the treatment of rectal and urogenital infections in MSM.

Patients and methods

This open-label, prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan from January 2019 to August 2022. Patients with M. genitalium urogenital or rectal infections were included. The patients were treated with sitafloxacin 200 mg daily for 7 days. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations.

Results

In total, 180 patients (median age, 35 years) were included in this study, of whom 77.0% (97/126) harboured parC mutations, including 71.4% (90/126) with G248T(S83I) in parC, and 22.5% (27/120) harboured gyrA mutations. The median time to test of cure was 21 days. The overall microbiological cure rate was 87.8%. The cure rate was 100% for microbes harbouring parC and gyrA WTs, 92.9% for microbes harbouring parC G248T(S83I) and gyrA WT, and 41.7% for microbes harbouring parC G248T(S83I) and gyrA with mutations. The cure rate did not differ significantly between urogenital and rectal infection (P = 0.359).

Conclusions

Sitafloxacin monotherapy was highly effective against infection caused by M. genitalium, except strains with combined parC and gyrA mutations. Sitafloxacin monotherapy can be used as a first-line treatment for M. genitalium infections in settings with a high prevalence of parC mutations and a low prevalence of gyrA mutations.
Improved adaptive thin-layer inversion for semi-airborne transient electromagnetic method
Authors: Xian Yougong , Lan Riyan , Liu Yuchao , Li Dunren , Yang Jing , Sun Huaifeng
Published: June 2023

To improve the resolution of electromagnetic inversion for thin layers, electromagnetic one-dimensional inversion was studied. The smooth conductivity model produced by Occam's inversion cannot accurately represent the information of the subterranean thin resistive layers, leading to erroneous inversion findings. The existing thin resistive layers’ inversion method sets the model constraint term at the thin resistive layers to 0, resulting in abrupt changes in resistivity values. Given these problems, we proposed an adaptive roughness matrix calculation method to improve the thin, low-resistive-layer resolution. The resistivity difference between neighboring layers of the updated inversion model determines the roughness matrix, allowing for the realization of adaptive inversion of the thin layer. It achieves semi-airborne transient electromagnetic enhanced adaptive thin-layer inversion and automatically manages the model constraint term. The calculation of the synthetic model demonstrates that the improved adaptive thin-layer inversion method does not need to know the thin, low-resistive layers information in advance. The model can produce appropriate inversion results regardless of the presence of thin, low-resistive layers. Finally, the drilling results are consistent with the inversed appearance of the semi-airborne transient electromagnetic field data. Other geophysical adaptive thin resistive layers inversion can also benefit from this paper's findings.
Satisfaction on educational training quality amongst college pharmacist alumni in Vietnam
Authors: Tran Ba Kien , Vu Thi Huong , Pham Duy Toan , Huynh Duyen Thi My , De Tran Van
Published: June 2023

Objectives

This study aimed to determine the factors affecting the satisfaction of 3-year-programme college pharmacy alumni on training/educational quality at a pharmacy college in Vietnam.

Methods

A cross-sectional research using a purposive sampling method was conducted on the alumni who had recently graduated in 2020 of a pharmacy college in Hai Duong, Vietnam. Data collection was conducted in two phases from November 2021 to January 2022, with the first phase being an online survey through Google Forms and the second phase being phone interviews and the use of the Zalo application. The quality of educational training was evaluated using 21 items, with an additional item designated for overall satisfaction. Exploratory factor analysis identified the four factors from the 21 items assessing training quality, whereas multivariate regression analysis determined the relationship between satisfaction factors and the overall satisfaction.

Results

A total of 282 complete records were obtained. The college pharmacist alumni’s satisfaction with the training qualities is influenced by four main factors, with internal consistency assessed using Cronbach’s alpha (α): the training staff (α = 0.93), the facilities and environment qualities (α = 0.91), the training programmes (α = 0.88) and the administrative formalities and support activities (α = 0.84). All factors had a positive impact on alumni satisfaction, the training staff factor (β = 0.460, P < 0.001) had the greatest impact on the alumni satisfaction.

Conclusions

This study identified four factors affecting the satisfaction of college pharmacy alumni on training quality, including (1) the training staff, (2) the facilities and environmental qualities, (3) the training programmes and (4) the administrative formalities and support activities. To enhance training quality and alumni satisfaction, educational institutions should focus on innovating the teaching methods of the faculty, shifting from traditional teaching methods to active teaching methods that make lectures dynamic and help students develop necessary skills, as well as organizing training sessions and practical visits to improve specialized knowledge and practical experience for the faculty.
On the causal interpretation of randomised interventional indirect effects
Authors: Miles Caleb H
Published: June 2023

Identification of standard mediated effects such as the natural indirect effect relies on heavy causal assumptions. By circumventing such assumptions, so-called randomised interventional indirect effects have gained popularity in the mediation literature. Here, I introduce properties one might demand of an indirect effect measure in order for it to have a true mediational interpretation. For instance, the sharp null criterion requires an indirect effect measure to be null whenever no individual-level indirect effect exists. I show that without stronger assumptions, randomised interventional indirect effects do not satisfy such criteria. I additionally discuss alternative causal interpretations of such effects.
Capacity building fees provisions of the Kurdistan region production sharing contracts as a mandatory corporate social responsibility tool
Authors: Salih Rdhwan Shareef
Published: June 2023

Due to corporate social responsibility (CSR), oil companies operate in socially responsible ways and engage more with local communities to ensure environmental protection and community welfare. In the past few years, the Kurdistan Region paid great attention to CSR. The main aim of this study is to provide a critical analysis of the CSR legal framework of the Kurdistan Region and survey the impact of CSR implementation on economic growth in Kurdistan, with a view to ascertain legal complications and underlining the weaknesses. The study clarifies that CSR is not limited to purely voluntary undertakings by companies but extends to mandatory government regulation and contractual commitments. In the Kurdistan Region, there is no legislation to make CSR mandatory or regulate CSR, and there is no penalty for non-complying companies. However, most of Kurdistan’s available production sharing contracts (PSCs) oblige contractors to pay capacity building bonuses and payments but due to the lack of legal regulation, their adopted amounts and types vary, and a number of PSCs require no capacity building bonus. Finally, the study suggests that CSR should be enforced by issuing a specific law and also propounds numerous recommendations for the Kurdistan Region to minimize legal contentions and problems relating to CSR.
One step further toward a crop CO2-concentrating mechanism
Authors: Findinier Justin , Grossman Arthur R
Published: June 2023

This article comments on:

Förster B, Rourke LM, Weerasooriya HN, Pabuayon ICM, Rolland V, Au EK, Bala S, Bajsa-Hirschel J, Kaines S, Kasili RW, LaPlace LM, Machingura MC, Massey B, Rosati VC, Stuart-Williams H, Badger MR, Price GD, Moroney JV. 2023. The Chlamydomonas reinhardtii chloroplast envelope protein LCIA transports bicarbonate in planta. Journal of Experimental Botany 74, 3651–3666
First test of the consistency relation for the large-scale structure using the anisotropic three-point correlation function of BOSS DR12 galaxies
Authors: Sugiyama Naonori S , Yamauchi Daisuke , Kobayashi Tsutomu , Fujita Tomohiro , Arai Shun , Hirano Shin’ichi , Saito Shun , Beutler Florian , Seo Hee-Jong
Published: June 2023

We present, for the first time, an observational test of the consistency relation for the large-scale structure (LSS) of the Universe through a joint analysis of the anisotropic two- and three-point correlation functions (2PCF and 3PCF) of galaxies. We parameterize the breakdown of the LSS consistency relation in the squeezed limit by Es, which represents the ratio of the coefficients of the shift terms in the second-order density and velocity fluctuations. Es ≠ 1 is a sufficient condition under which the LSS consistency relation is violated. A novel aspect of this work is that we constrain Es by obtaining information about the non-linear velocity field from the quadrupole component of the 3PCF without taking the squeezed limit. Using the galaxy catalogues in the Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 12, we obtain $E_{\rm s} = -0.92_{-3.26}^{+3.13}$, indicating that there is no violation of the LSS consistency relation in our analysis within the statistical errors. Our parameterization is general enough that our constraint can be applied to a wide range of theories, such as multicomponent fluids, modified gravity theories, and their associated galaxy bias effects. Our analysis opens a new observational window to test the fundamental physics using the anisotropic higher-order correlation functions of galaxy clustering.
A catalogue of radio supernova remnants and candidate supernova remnants in the EMU/POSSUM Galactic pilot field
Authors: Ball Brianna D , Kothes Roland , Rosolowsky Erik , West Jennifer , Becker Werner , Filipović Miroslav D , Gaensler B M , Hopkins Andrew M , Koribalski Bärbel , Landecker Tom , Leahy Denis , Marvil Joshua , Sun Xiaohui , Bufano Filomena , Carretti Ettore , Ingallinera Adriano , Van Eck Cameron L , Willis Tony
Published: June 2023

We use data from the pilot observations of the EMU/POSSUM surveys to study the ‘missing supernova remnant (SNR) problem’, the discrepancy between the number of Galactic SNRs that have been observed, and the number that are estimated to exist. The Evolutionary Map of the Universe (EMU) and the Polarization Sky Survey of the Universe’s Magnetism (POSSUM) are radio sky surveys that are conducted using the Australian Square Kilometre Array Pathfinder (ASKAP). We report on the properties of seven known SNRs in the joint Galactic pilot field, with an approximate longitude and latitude of 323° ≤ l ≤ 330° and −4° ≤ b ≤ 2°, respectively, and identify 21 SNR candidates. Of these, four have been previously identified as SNR candidates, three were previously listed as a single SNR, 13 have not been previously studied, and one has been studied in the infrared. These are the first discoveries of Galactic SNR candidates with EMU/POSSUM and, if confirmed, they will increase the SNR density in this field by a factor of 4. By comparing our SNR candidates to the known Galactic SNR population, we demonstrate that many of these sources were likely missed in previous surveys due to their small angular size and/or low surface brightness. We suspect that there are SNRs in this field that remain undetected due to limitations set by the local background and confusion with other radio sources. The results of this paper demonstrate the potential of the full EMU/POSSUM surveys to uncover more of the missing Galactic SNR population.
CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins
Authors: Chen Mengqian , Li Jing , Zhang Li , Wang Lili , Cheng Chen , Ji Hao , Altilia Serena , Ding Xiaokai , Cai Guoshuai , Altomare Diego , Shtutman Michael , Byrum Stephanie D , Mackintosh Samuel G , Feoktistov Alexey , Soshnikova Nataliya , Mogila Vladislav A , Tatarskiy Victor , Erokhin Maksim , Chetverina Darya , Prawira Angga , Ni Yi , Urban Stephan , McInnes Campbell , Broude Eugenia V , Roninson Igor B
Published: June 2023

We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small group of genes, most of which were inducible by serum or PKC stimulation. Prolonged CDK8/19 inhibition or mutagenesis upregulated a larger gene set, along with a post-transcriptional increase in the proteins comprising the core Mediator complex and its kinase module. Regulation of both RNA and protein expression required CDK8/19 kinase activities but both enzymes protected their binding partner cyclin C from proteolytic degradation in a kinase-independent manner. Analysis of isogenic cell populations expressing CDK8, CDK19 or their kinase-inactive mutants revealed that CDK8 and CDK19 have the same qualitative effects on protein phosphorylation and gene expression at the RNA and protein levels, whereas differential effects of CDK8 versus CDK19 knockouts were attributable to quantitative differences in their expression and activity rather than different functions.
Efficacy and safety of prolonged water fasting: a narrative review of human trials
Authors: Ezpeleta Mark , Cienfuegos Sofia , Lin Shuhao , Pavlou Vasiliki , Gabel Kelsey , Varady Krista A
Published: June 2023

The goal of this narrative review is to summarize the effects of prolonged fasting on various metabolic health measures, including body weight, blood pressure, plasma lipids, and glycemic control. Prolonged fasting is characterized by consciously eating little to no food or caloric beverages for several days to weeks. Results reveal that prolonged fasting for 5–20 days produces potent increases in circulating ketones, and mild to moderate weight loss of 2–10%. Approximately two-thirds of the weight lost is lean mass, and one-third is fat mass. The excessive lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern. Systolic and diastolic blood pressure consistently decreased with prolonged fasting. However, the impact of these protocols on plasma lipids is less clear. While some trials demonstrate decreases in LDL cholesterol and triglycerides, others show no benefit. With regard to glycemic control, reductions in fasting glucose, fasting insulin, insulin resistance, and glycated hemoglobin (HbA1c) were noted in adults with normoglycemia. In contrast, these glucoregulatory factors remained unchanged in patients with type 1 or type 2 diabetes. The effects of refeeding were also examined in a few trials. It was shown that 3–4 months after the fast was completed, all metabolic benefits were no longer observed, even when weight loss was maintained. With regard to adverse events, metabolic acidosis, headaches, insomnia, and hunger were observed in some studies. In summary, prolonged fasting appears to be a moderately safe diet therapy that can produce clinically significant weight loss (>5%) over a few days or weeks. However, the ability of these protocols to produce sustained improvements in metabolic markers warrants further investigation.
Children at Familial High risk of Schizophrenia and Bipolar Disorder Exhibit Altered Connectivity Patterns During Pre-attentive Processing of an Auditory Prediction Error
Authors: Larsen Kit Melissa , Madsen Kathrine Skak , Ver Loren van Themaat Anna Hester , Thorup Anne Amalie Elgaard , Plessen Kerstin Jessica , Mors Ole , Nordentoft Merete , Siebner Hartwig Roman
Published: June 2023

Background and Hypothesis

Individuals with schizophrenia or bipolar disorder have attenuated auditory mismatch negativity (MMN) responses, indicating impaired sensory information processing. Computational models of effective connectivity between brain areas underlying MMN responses show reduced connectivity between fronto-temporal areas in individuals with schizophrenia. Here we ask whether children at familial high risk (FHR) of developing a serious mental disorder show similar alterations.

Study Design

We recruited 67 children at FHR for schizophrenia, 47 children at FHR for bipolar disorder as well as 59 matched population-based controls from the Danish High Risk and Resilience study. The 11–12-year-old participants engaged in a classical auditory MMN paradigm with deviations in frequency, duration, or frequency and duration, while we recorded their EEG. We used dynamic causal modeling (DCM) to infer on the effective connectivity between brain areas underlying MMN.

Study Results

DCM yielded strong evidence for differences in effective connectivity among groups in connections from right inferior frontal gyrus (IFG) to right superior temporal gyrus (STG), along with differences in intrinsic connectivity within primary auditory cortex (A1). Critically, the 2 high-risk groups differed in intrinsic connectivity in left STG and IFG as well as effective connectivity from right A1 to right STG. Results persisted even when controlling for past or present psychiatric diagnoses.

Conclusions

We provide novel evidence that connectivity underlying MMN responses in children at FHR for schizophrenia and bipolar disorder is altered at the age of 11–12, echoing findings that have been found in individuals with manifest schizophrenia.
The financialization of corporate venture capital investment? The corporation as a venture capitalist
Authors: Szalavetz Andrea , Sauvage Nicolas
Published: June 2023

Recent trends in corporate venture capital (CVC) activities have added to the size and complexity of the financial system. Intuition suggests that in a period marked by spectacularly increasing start-up valuations, the opportunity to earn large capital gains increases the importance of corporate investors’ financial motivations. Drawing on interviews with 12 Silicon Valley-based CVC units of global industrial companies, we examine if new trends in CVC investment represent a diversion from incumbents’ traditional focus on improving the competitive advantage of their core businesses. Building on the theory of the financialization of non-financial companies, we investigate the relationship between the strategic and financial motivations of CVC investing. We extend theory by distinguishing between developments at the extensive and intensive margins. We argue that the commonly applied quantitative measures capture financialization only at the extensive margin. Qualitative data indicate that the hypothesis of financialization does not hold at the intensive margin.
Boosting work through welfare? Individual-level employment outcomes of social investment across European welfare states through the Great Recession
Authors: Ronchi Stefano
Published: June 2023

Given the heterogeneity of European welfare states, governments’ efforts in ‘social investment’ reform may reap different outcomes in different national contexts. Through multi-level modelling based on longitudinal microdata from the EU Statistics on Income and Living Conditions (2004–2013) and on country-level policy indicators, this article assesses: whether citizens of countries that put higher budgetary efforts into social investment have better employment prospects and whether increasing such efforts over time improves employment chances within a country; whether people living in social investment-oriented welfare states maintained higher employment chances in the years of the Great Recession; whether micro-level employment outcomes depend on (in-)complementarities between investment- and protection-oriented policies. The results reveal that the most social investment-oriented welfare states show higher individual-level employment chances, which they were able to preserve during the Great Recession. However, increasing resources on social investments does not always yield empirically discernible returns over the short-to-medium term.
Experimental models of fatty liver diseases: Status and appraisal
Authors: Wang Hua , Shen Haiyuan , Seo Wonhyo , Hwang Seonghwan
Published: June 2023

Fatty liver diseases, including alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease nonalcoholic fatty liver disease (NAFLD), affect a large number of people worldwide and become one of the major causes of end-stage liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC). Unfortunately, there are currently no approved pharmacological treatments for ALD or NAFLD. This situation highlights the urgent need to explore new intervention targets and discover effective therapeutics for ALD and NAFLD. The lack of properly validated preclinical disease models is a major obstacle to the development of clinical therapies. ALD and NAFLD models have been in the development for decades, but there are still no models that recapitulate the full spectrum of ALD and NAFLD. Throughout this review, we summarize the current in vitro and in vivo models used for research on fatty liver diseases and discuss the advantages and limitations of these models.
Nutrient Supplementation Improves Contact Lens–Induced Corneal Cell Damage Based on a SIRC Cellular Model
Authors: Chang Wan-Hsin , Tsai Meng-Chun , Liu Pei-Yi , Lu Chien-Ju , Howard Hsu Yuan-Hao
Published: June 2023

Objectives:

The long-term use of contact lenses may damage the structure of the ocular surface and cause metabolic disorders in corneal cells. Vitamins and amino acids help maintain the physiological function of the eye. In the present study, the effects of nutrient (vitamin and amino acid) supplementation on corneal cell repair after contact lens–induced damage was investigated.

Methods:

High-performance liquid chromatography was used to quantify the nutrient contents of minimum essential medium, and the MTT assay was used to measure the viability of corneal cells. A Statens Seruminstitut rabbit cornea cellular model was established to simulate contact lens–induced keratopathy and investigate the effects of vitamin and amino acid supplementations on corneal cell repair.

Results:

The high water content lens group (78%) has a cell viability as high as 83.3%, whereas the cell viability of the low water content lens group (38%) is only 51.6%. The 32.0% difference between the two groups confirms the correlation between water content of lens and corneal viability.

Conclusions:

Vitamin B2, vitamin B12, asparagine, and taurine supplementation may help improve contact lens–induced damage.
Vulvar and Vaginal Graft Versus Host Disease After Allogeneic Stem Cell Transplant—A Systematic Review
Authors: Preston Marta , Richards Anthony
Published: June 2023

Objective

To conduct a systematic literature search to identify and determine the prevalence, signs and symptoms, and clinical management of vulvar and vaginal graft versus host disease (GVHD).

Methods

A systematic literature search of articles from 1993 to August 2022 was performed. Studies were included if full text was available in the English language and provided reports on female subjects with more than four patients. Review articles, conference abstracts, case reports, and case series of less than 5 patients were excluded. Included studies had their reference list searched for further manuscripts. Two authors reviewed the search results and independently identified studies that met the selection criteria and summarized available data.

Results

There were 29 studies available in the literature that met the inclusion criteria. There was a high risk of bias within the available literature. The prevalence of vulval and vaginal GVHD varied between 27% and 66% of women after allogeneic stem cell transplant. Other organ GVHD, most commonly the skin, mouth, and eyes, may be present concurrently in these patients, or they may be asymptomatic. Specialist gynecology review, topical estrogen, topical steroids, topical immunosuppression, and vaginal dilatation led to a reduction in complications associated with the condition, and surgery was helpful in some severe refractory cases. These patients remain at higher risk of developing cervical dysplasia, and regular human papillomavirus screening is recommended.

Conclusions

Female genital GVHD is a rare phenomenon. Early, coordinated, and regular gynecological reviews after stem cell transplant are essential to reduce the long-term complications.
Characteristics of Patients With Behçet Disease From the Van Province, Eastern Turkey
Authors: Oguz Emin , Bektaş Murat
Published: June 2023

Background

Behçet disease (BD) is a chronic inflammatory systemic disease that affects skin mucosa, joints, eyes, and blood vessels. Behçet disease shows some clinical differences in terms of disease manifestations and prognosis among the Silk Road countries, as well as various ethnicities even in the same country. In this study, we aimed to evaluate the clinical features and disease course of BD using cluster analysis in Van province, Eastern Turkey.

Methods

This study was carried out in a tertiary referral center in Van province, by reviewing medical records. Seven disease manifestations were included to the cluster analysis as follows: mucocutaneous findings (oral ulcer, genital ulcer, erythema nodosum–like lesions, pseudofolliculitis), uveitis, superficial thrombophlebitis, musculoskeletal involvement, gastrointestinal system involvement, vascular involvement, and parenchymal central nervous system involvement.

Results

We identified 467 patients. After the exclusion of 6 patients who had missing data and 17 patients who did not live in Van, 444 patients (59.2% male) included into the study. Meeting the International Study Group and the International Criteria for Behçet Disease criteria were 91.6% and 96%, respectively, and 91.3% (n = 379/415) of these patients met both criteria. Four clusters were identified in the analyses: 132 patients (31.2%) in vascular (C1), 66 patients (15.6%) in ocular (C2), 60 patients (14.2%) in musculoskeletal (C3), and 165 patients (39%) in mucocutaneous (C4) clusters. Male gender (p = 0.002; odds ratio [OR], 6.5; 95% confidence interval [CI], 2–21.4), superficial thrombophlebitis (p = 0.001; OR, 4.7; 95% CI, 1.9–11.4), and uveitis (p = 0.01; OR, 3.6; 95% CI, 1.3–9.9) were associated with vascular involvement in multivariate analysis.

Conclusions

In our study, 4 clusters were detected in patients with BD from Van province. The prevalence of severe manifestations of BD may be related to genetic or environmental factors, such as differences in ethnicity and/or geographical differences. Despite the higher proportion of patients with a more severe disease, a favorable outcome was observed in our cohort.
Computed Tomography 2.0
Authors: Lell Michael , Kachelrieß Marc
Published: June 2023

Computed tomography (CT) dramatically improved the capabilities of diagnostic and interventional radiology. Starting in the early 1970s, this imaging modality is still evolving, although tremendous improvements in scan speed, volume coverage, spatial and soft tissue resolution, as well as dose reduction have been achieved. Tube current modulation, automated exposure control, anatomy-based tube voltage (kV) selection, advanced x-ray beam filtration, and iterative image reconstruction techniques improved image quality and decreased radiation exposure. Cardiac imaging triggered the demand for high temporal resolution, volume acquisition, and high pitch modes with electrocardiogram synchronization. Plaque imaging in cardiac CT as well as lung and bone imaging demand for high spatial resolution. Today, we see a transition of photon-counting detectors from experimental and research prototype setups into commercially available systems integrated in patient care. Moreover, with respect to CT technology and CT image formation, artificial intelligence is increasingly used in patient positioning, protocol adjustment, and image reconstruction, but also in image preprocessing or postprocessing. The aim of this article is to give an overview of the technical specifications of up-to-date available whole-body and dedicated CT systems, as well as hardware and software innovations for CT systems in the near future.
Evaluation of Immunocompetence and Biomarkers of Tolerance in Chimeric and Immunosuppression-free Kidney Allograft Recipients
Authors: Leventhal Joseph R. , Galvin John , Ison Michael G. , Feng Chris Yuhsuen , Ding Ruchuang , Lee John R. , Li Carol , Mathew James M. , Gallon Lorenzo , Gibson Meg , Belshe Dianne , Tollerud David J. , Gornstein Eric , Suthanthiran Manikkam , Ildstad Suzanne T.
Published: June 2023

Background.

Thirty-seven patients have received a living-donor kidney transplant in a phase 2 study designed to induce tolerance with facilitated allogeneic hematopoietic stem cell transplant. The study protocol is based on tolerogenic CD8+/T-cell receptor− facilitating cells (FCR001; also including hematopoietic stem cells and αβ-T-cell receptor+ T cells) and low-dose, nonmyeloablative conditioning. Persistent chimerism allowing full immunosuppression (IS) withdrawal was achieved in 26 patients (time off IS 36–123 mo).

Methods.

We evaluated biomarkers of tolerance through urinary cell mRNA profiling and immunocompetence to respond to vaccination in these patients. We also assessed kidney function and metabolic parameters compared with standard-of-care patients on IS.

Results.

Persistently chimeric patients retained chimerism after removal of IS and remained rejection free without donor HLA–specific antibody development. The presence of donor chimerism at >50% correlated with a signature of tolerance in urinary cell mRNA profiles, with a uniquely elevated increase in the ratio of cytotoxic T lymphocyte–associated protein 4 to granzyme B mRNA. Tolerance was associated with protection from recurrence of immune-mediated causes of kidney disease. Tolerant participants were safely vaccinated, developed protective immune responses, and did not lose chimerism after vaccination. When compared with kidney transplant recipients treated with standard IS, tolerant participants showed stable kidney function and reduced medication use for hypertension and hyperlipidemia.

Conclusions.

These results suggest that elimination of IS has distinct advantages in living-donor kidney allograft recipients.
The ups and downs of biological oscillators: a comparison of time-delayed negative feedback mechanisms
Authors: Rombouts Jan , Verplaetse Sarah , Gelens Lendert
Published: June 2023

Many biochemical oscillators are driven by the periodic rise and fall of protein concentrations or activities. A negative feedback loop underlies such oscillations. The feedback can act on different parts of the biochemical network. Here, we mathematically compare time-delay models where the feedback affects production and degradation. We show a mathematical connection between the linear stability of the two models, and derive how both mechanisms impose different constraints on the production and degradation rates that allow oscillations. We show how oscillations are affected by the inclusion of a distributed delay, of double regulation (acting on production and degradation) and of enzymatic degradation.
The biomechanics of tooth strength: testing the utility of simple models for predicting fracture in geometrically complex teeth
Authors: Sender Rachel S. , Strait David S.
Published: June 2023

Teeth must fracture foods while avoiding being fractured themselves. This study evaluated dome biomechanical models used to describe tooth strength. Finite-element analysis (FEA) tested whether the predictions of the dome models applied to the complex geometry of an actual tooth. A finite-element model was built from microCT scans of a human M
3
. The FEA included three loading regimes simulating contact between (i) a hard object and a single cusp tip, (ii) a hard object and all major cusp tips and (iii) a soft object and the entire occlusal basin. Our results corroborate the dome models with respect to the distribution and orientation of tensile stresses, but document heterogeneity of stress orientation across the lateral enamel. This implies that high stresses might not cause fractures to fully propagate between cusp tip and cervix under certain loading conditions. The crown is most at risk of failing during hard object biting on a single cusp. Geometrically simple biomechanical models are valuable tools for understanding tooth function but do not fully capture aspects of biomechanical performance in actual teeth whose complex geometries may reflect adaptations for strength.
Reemergence of Acute ischemic Stroke hospitalizations in the United States from 2010 to 2020
Authors: Elbayomy Ahmed M. , Kim Jason J , Ammanuel Simon G , Bradbury Edward L. , Dempsey Robert J , Ahmed Azam S.
Published: June 2023

Background and Objectives

Stroke hospitalization rates in the United States are unequally distributed across the population. Factors such as age, race, socioeconomic status, and sex are associated with different hospitalization rates for acute ischemic stroke (AIS). This study aimed to review the patterns in these rates from 2010 to 2020.

Methods

The National Inpatient Sample (NIS) was used to analyze patterns in AIS hospitalizations in the United States between 2010 and 2020. The hospitalization rates were examined based on age, sex, race, region, stroke comorbidities, and income.

Results

The overall rate of AIS hospitalization increased from 230 to 254 per 100,000 individuals (+10.4%) between 2010 and 2020. Initially, the rates declined from 2010 to 2015 (230 to 227 per 100,000); however, from 2016 to 2020, the AIS hospitalization rates (AIS-HR) increased (242 to 254 per 100,000). The rate of AIS hospitalization increased significantly for individuals aged 25–44 years (25–37 per 100,000, +48.0%) and 45–65 years (171–235 per 100,000, +37.4%). AIS hospitalization rates remained relatively stable for individuals aged 65– 84 years (669–688 per 100,000, +3.7%) and declined for those over 85 years (2005–1756 per 100,000, -12.4%). Among sex comparisons, AIS hospitalization rates were stable in women (241–250 per 100,000, +3.7%) and increased in men (270–308 per 100,000, +14.1%). In terms of race, Blacks had the highest age-adjusted yearly hospitalization rate (437), followed by Whites (215) and Hispanics (207) per 100,000 in 2020. There was a stepwise increase in AIS hospitalization rates based on the Charlson Comorbidity Index (CCI), with White, Black, and Hispanic populations having AIS hospitalization rates of CCI 0 and 1 (533, 434, and 233), CCI 2 (2197, 2555, and 2125), and CCI ≥ 3 (5283, 5724, and 4767) per 100,000, respectively.

Discussion

Although the overall AIS hospitalization rate increased between 2010 and 2020, there was an initial decline until 2015, followed by a resurgence. This resurgence in AIS hospitalization rates was driven by greater underlying comorbidities, with disproportionate increases observed in Black and Hispanic populations. Further population analyses and cohort studies are required to confirm our findings.
Thermal compensation reduces DNA damage in UV-exposed amphibian larvae: Implications for high latitudinal and altitudinal species
Authors: Hird Coen , Cramp Rebecca L. , Franklin Craig E.
Published: June 2023

1. Increases in ultraviolet radiation (UVR) correlate spatially and temporally with global amphibian population declines and interact with other stressors such as disease and temperature. Declines have largely occurred in high-altitude areas associated with greater UVR and cooler temperatures.

2. UVR is a powerful mutagenic harming organisms largely by damaging DNA. When acutely exposed to UVR at cool temperatures, amphibian larvae have increased levels of DNA damage. Amphibians may be able to compensate for the depressive effects of temperature on DNA damage through thermal acclimatisation, but it is unknown whether they or other ectotherms have this capacity.

3. We reared striped marsh frog larvae (Limnodynastes peronii) in warm (25°C) and cool (15°C) temperatures under either a low or moderate daily dose of UVR (10 and 40 µW cm-2UV-B for 1 h at midday, respectively) for 18-20 days and then measured immediate DNA damage resulting from an acute high UVR dose (80 µW cm-2UV-B for 1.5 h) at a range of test temperatures (10, 15, 20, 25, and 30°C).

4. Larvae acclimated to 15°C and exposed to UVR at 15°C completely compensated UVR-induced DNA damage compared with 25°C acclimated larvae exposed to UVR at 25°C. Additionally, warm-acclimated larvae had higher CPDs than cold-acclimated larvae across test temperatures, which indicated a cost of living in warmer temperatures. In contrast, larvae reared under chronic elevated UVR levels showed no evidence of UVR acclimation resulting in lower DNA damage following an acute high UVR exposure.

5. Our finding that thermal acclimation inL. peroniilarvae compensated UVR-induced DNA damage at low temperatures suggested that aquatic ectotherms living in cool temperatures may be more resilient to high UVR than previously realised.

6. We suggested individuals or species with less capacity for thermal acclimation of DNA repair mechanisms may be more at risk if exposed to changing thermal and UVR exposure regimes but cautioned that thermal acclimation of DNA repair mechanisms may not always be beneficial.