bluuebunny/crossref_metadata_2025 huggingface dataset:
The composite quality score for the appraisal of prospective controlled clinical therapy trials in systematic reviews and its limits
Authors: Mickenautsch Steffen , Rupf Stefan , Yengopal Veerasamy
Published: June 2023

Systematic reviews of prospective controlled clinical therapy trials are one of the most important sources of information in modern medicine. Besides the systematic search for and statistical pooling of current clinical trial data for a particular type of therapy, systematic reviews also have the task of appraising the quality of trial results. The quality of trial results may be diminished by low internal trial validity, due to systematic error (bias). A high risk of bias may likely cause the reported trial results to be diverted from the actual true therapeutic effect and thus render it unsuitable for clinical guidance. According to the Cochrane Collaboration, the risk of bias in clinical therapy trials should be assessed using its Risk of Bias tool, Version 2 (RoB 2). However, the tool has been established to have poor inter-rater reliability, with a limited empirical evidence base and described as complex and demanding. Against this background, the composite quality score (CQS) has been developed as a possible alternative trial appraisal tool, characterised by high epistemic rigour, empirical evidence base, inter-rater reliability and ease of use. This article presents the current evidence of the CQS and its limitations.
What defines a great surgeon? A survey study confronting perspectives
Authors: Luscan Romain , Malheiro Emeline , Sisso Fiona , Wartelle Sébastien , Parc Yann , Fauroux Brigitte , Bégué Thierry , Johanet Hubert , Denoyelle Françoise , Garabédian Erea-Noël , Simon François
Published: June 2023

Background

The definition of a great surgeon is usually reported by surgeons themselves. The objective of the study was to define a multifaceted definition of a great surgeon, by confronting patients', healthcare workers', and surgeons' perspectives.

Study design

An online open-ended questionnaire was created to identify three qualities and three shortcomings defining a great surgeon. Age, gender, and profession of respondents were collected. Responses with a similar meaning were combined into word groups and labeled within four themes: human qualities, technical surgical skills (TSS), non-technical skills (NTS), and knowledge. Multivariate analyses were conducted between themes and respondent characteristics.

Results

Four thousand seven hundred and sixty qualities and 4,374 shortcomings were obtained from 1,620 respondents including 385 surgeons, 291 patients, 565 operating theater (OT) health professionals, and 379 non-OT health professionals. The main three qualities were dexterity (54% of respondents), meticulousness (18%), and empathy (18%). There was no significant difference between professional categories for TSS. Compared with surgeons, non-OT health professionals and patients put more emphasis on human qualities (29 vs. 39% and 42%, respectively, p < .001). OT health professionals referred more to NTS than surgeons (35 vs. 22%, p < 0.001). Knowledge was more important for surgeons (19%) than for all other professional categories (p < 0.001).

Conclusions

This survey illustrates the multifaceted definition of a great surgeon. Even if dexterity is a major quality, human qualities are of paramount importance. Knowledge seems to be underestimated by non-surgeons, although it essential to understand the disease and preparing the patient and OT team for the procedure.
Wood fibers are a crucial microhabitat for cellulose- and xylan- degrading bacteria in the hindgut of the wood-feeding beetle Odontotaenius disjunctus
Authors: Schwarz Melbert , Beza-Beza Cristian F. , Mikaelyan Aram
Published: June 2023

Introduction

Wood digestion in insects relies on the maintenance of a mosaic of numerous microhabitats, each colonized by distinct microbiomes. Understanding the division of digestive labor between these microhabitats- is central to understanding the physiology and evolution of symbiotic wood digestion. A microhabitat that has emerged to be of direct relevance to the process of lignocellulose digestion is the surface of ingested plant material. Wood particles in the guts of some termites are colonized by a specialized bacterial fiber-digesting microbiome, but whether this represents a widespread strategy among insect lineages that have independently evolved wood-feeding remains an open question.

Methods

In this study, we investigated the bacterial communities specifically associated with wood fibers in the gut of the passalid beetle Odontotaenius disjunctus. We developed a Percoll-based centrifugation method to isolate and enrich the wood particles from the anterior hindgut, allowing us to access the wood fibers and their associated microbiome. We then performed assays of enzyme activity and used short-read and long-read amplicon sequencing of the 16S rRNA gene to identify the composition of the fiber-associated microbiome.

Results

Our assays demonstrated that the anterior hindgut, which houses a majority of the bacterial load, is an important site for lignocellulose digestion. Wood particles enriched from the anterior hindgut contribute to a large proportion of the total enzyme activity. The sequencing revealed that O. disjunctus, like termites, harbors a distinct fiber-associated microbiome, but notably, its community is enriched in insect-specific groups of Lactococcus and Turicibacter.

Discussion

Our study underscores the importance of microhabitats in fostering the complex symbiotic relationships between wood-feeding insects and their microbiomes. The discovery of distinct fiber-digesting symbionts in O. disjunctus, compared to termites, highlights the diverse evolutionary paths insects have taken to adapt to a challenging diet.
Clinical metagenomics—challenges and future prospects
Authors: Batool Maliha , Galloway-Peña Jessica
Published: June 2023

Infections lacking precise diagnosis are often caused by a rare or uncharacterized pathogen, a combination of pathogens, or a known pathogen carrying undocumented or newly acquired genes. Despite medical advances in infectious disease diagnostics, many patients still experience mortality or long-term consequences due to undiagnosed or misdiagnosed infections. Thus, there is a need for an exhaustive and universal diagnostic strategy to reduce the fraction of undocumented infections. Compared to conventional diagnostics, metagenomic next-generation sequencing (mNGS) is a promising, culture-independent sequencing technology that is sensitive to detecting rare, novel, and unexpected pathogens with no preconception. Despite the fact that several studies and case reports have identified the effectiveness of mNGS in improving clinical diagnosis, there are obvious shortcomings in terms of sensitivity, specificity, costs, standardization of bioinformatic pipelines, and interpretation of findings that limit the integration of mNGS into clinical practice. Therefore, physicians must understand the potential benefits and drawbacks of mNGS when applying it to clinical practice. In this review, we will examine the current accomplishments, efficacy, and restrictions of mNGS in relation to conventional diagnostic methods. Furthermore, we will suggest potential approaches to enhance mNGS to its maximum capacity as a clinical diagnostic tool for identifying severe infections.
Hypovirus infection induces proliferation and perturbs functions of mitochondria in the chestnut blight fungus
Authors: Wang Jinzi , Quan Rui , He Xipu , Fu Qiang , Tian Shigen , Zhao Lijiu , Li Shuangcai , Shi Liming , Li Ru , Chen Baoshan
Published: June 2023

Introduction

The chestnut blight fungus, Cryphonectria parasitica, and hypovirus have been used as a model to probe the mechanism of virulence and regulation of traits important to the host fungus. Previous studies have indicated that mitochondria could be the primary target of the hypovirus.

Methods

In this study, we report a comprehensive and comparative study comprising mitochondrion quantification, reactive oxygen species (ROS) and respiratory efficiency, and quantitative mitochondrial proteomics of the wild-type and virus-infected strains of the chestnut blight fungus.

Results and discussion

Our data show that hypovirus infection increases the total number of mitochondria, lowers the general ROS level, and increases mitochondrial respiratory efficiency. Quantification of mitochondrial proteomes revealed that a set of proteins functioning in energy metabolism and mitochondrial morphogenesis, as well as virulence, were regulated by the virus. In addition, two viral proteins, p29 and p48, were found to co-fractionate with the mitochondrial membrane and matrix. These results suggest that hypovirus perturbs the host mitochondrial functions to result in hypovirulence.
Toward the use of mixed microbial cultures for the biological production of adipic and levulinic acid
Authors: Pinto-Ibieta Fernanda , Cea Mara , Serrano Antonio , Felissia Fernando E. , Area María Cristina , Cabrera Francisco , Ciudad Gustavo
Published: June 2023

Biological synthesis of high added-value compounds like adipic acid (AA), levulinic acid (LA), or polyhydroxybutyrate (PHB) using pure culture has been separately reported. However, pure culture requires sterile conditions and the use of specific carbon sources resulting in high operating costs. Different alternatives based on the use of mixed microbial cultures (MMC) have been explored to resolve this problem. MMC have been widely reported for the production of PHB, but scarcely reported for LA production and never for AA synthesis. This work presents a novel strategy for the co-production of AA LA, and PHB using MMC. The strategy consists in selecting an MMC producer of AA, LA and PHB from an inoculum obtained from a wastewater treatment plant, which is then subjected to the feast and famine culture strategy in a sequential batch reactor, coupled with a batch reactor step to enhance the accumulation of AA and LA. The results showed that the MMC could produce a 16 ± 2, 23 ± 1 and 5 ± %1 (g compound/g volatile solids) of AA, LA and PHB, respectively, using a non-fermented residual biomass rich in pentose, namely synthetic hemicellulose hydrolysate (SHH) as the carbon source. These results contribute to generating future research to better understand and optimise the biosynthesis of these compounds by MMC.
Bidirectional plasticity of GABAergic tonic inhibition in hippocampal somatostatin- and parvalbumin-containing interneurons
Authors: Wyroślak Marcin , Dobrzański Grzegorz , Mozrzymas Jerzy W.
Published: June 2023

GABAA receptors present in extrasynaptic areas mediate tonic inhibition in hippocampal neurons regulating the performance of neural networks. In this study, we investigated the effect of NMDA-induced plasticity on tonic inhibition in somatostatin- and parvalbumin-containing interneurons. Using pharmacological methods and transgenic mice (SST-Cre/PV-Cre x Ai14), we induced the plasticity of GABAergic transmission in somatostatin- and parvalbumin-containing interneurons by a brief (3 min) application of NMDA. In the whole-cell patch-clamp configuration, we measured tonic currents enhanced by specific agonists (etomidate or gaboxadol). Furthermore, in both the control and NMDA-treated groups, we examined to what extent these changes depend on the regulation of distinct subtypes of GABAA receptors. Tonic conductance in the somatostatin-containing (SST+) interneurons is enhanced after NMDA application, and the observed effect is associated with an increased content of α5-containing GABAARs. Both fast-spiking and non–fast-spiking parvalbumin-positive (PV+) cells showed a reduction of tonic inhibition after plasticity induction. This effect was accompanied in both PV+ interneuron types by a strongly reduced proportion of δ-subunit-containing GABAARs and a relatively small increase in currents mediated by α5-containing GABAARs. Both somatostatin- and parvalbumin-containing interneurons show cell type-dependent and opposite sign plasticity of tonic inhibition. The underlying mechanisms depend on the cell-specific balance of plastic changes in the contents of α5 and δ subunit-containing GABAARs.
Combining high dose therapy, bilateral motor priming, and vagus nerve stimulation to treat the hemiparetic upper limb in chronic stroke survivors: a perspective on enhancing recovery
Authors: King Erin C. , Pedi Elizabeth , Stoykov Mary Ellen , Corcos Daniel M. , Urday Sebastian
Published: June 2023

Stroke is a leading cause of disability worldwide and upper limb hemiparesis is the most common post-stroke disability. Recent studies suggest that clinically significant motor recovery is possible in chronic stroke survivors with severe impairment of the upper limb. Three promising strategies that have been investigated are (1) high dose rehabilitation therapy (2) bilateral motor priming and (3) vagus nerve stimulation. We propose that the future of effective and efficient upper limb rehabilitation will likely require a combination of these approaches.
Factors associated with stroke after COVID-19 vaccination: a statewide analysis
Authors: Nahab Fadi , Bayakly Rana , Sexton Mary Elizabeth , Lemuel-Clarke Manet , Henriquez Laura , Rangaraju Srikant , Ido Moges
Published: June 2023

Background

The objective of our study was to evaluate vaccine type, COVID-19 infection, and their association with stroke soon after COVID-19 vaccination.

Methods

In a retrospective cohort study, we estimated the 21-day post-vaccination incidence of stroke among the recipients of the first dose of a COVID-19 vaccine. We linked the Georgia Immunization Registry with the Georgia Coverdell Acute Stroke Registry and the Georgia State Electronic Notifiable Disease Surveillance System data to assess the relative risk of stroke by the vaccine type.

Results

Approximately 5 million adult Georgians received at least one COVID-19 vaccine between 1 December 2020 and 28 February 2022: 54% received BNT162b2, 41% received mRNA-1273, and 5% received Ad26.COV2.S. Those with concurrent COVID-19 infection within 21 days post-vaccination had an increased risk of ischemic (OR = 8.00, 95% CI: 4.18, 15.31) and hemorrhagic stroke (OR = 5.23, 95% CI: 1.11, 24.64) with no evidence for interaction between the vaccine type and concurrent COVID-19 infection. The 21-day post-vaccination incidence of ischemic stroke was 8.14, 11.14, and 10.48 per 100,000 for BNT162b2, mRNA-1273, and Ad26.COV2.S recipients, respectively. After adjusting for age, race, gender, and COVID-19 infection status, there was a 57% higher risk (OR = 1.57, 95% CI: 1.02, 2.42) for ischemic stroke within 21 days of vaccination associated with the Ad26.COV2.S vaccine compared to BNT162b2; there was no difference in stroke risk between mRNA-1273 and BNT162b2.

Conclusion

Concurrent COVID-19 infection had the strongest association with early ischemic and hemorrhagic stroke after the first dose of COVID-19 vaccination. Although not all determinants of stroke, particularly comorbidities, were considered in this analysis, the Ad26.COV2.S vaccine was associated with a higher risk of early post-vaccination ischemic stroke than BNT162b2.
Genetic impairment of folate metabolism regulates cortical interneurons and social behavior
Authors: Sadigurschi Noa , Scrift Gilad , Hirrlinger Johannes , Golan Hava M.
Published: June 2023

Introduction

The implications of folate deficiency in neuropsychiatric disorders were demonstrated in numerous studies. Genetic deficiency in a key folate metabolism enzyme, MTHFR, is an example of the interaction between genetic and environmental risk factors: the maternal MTHFR deficiency governs in-utero nutrient availability, and the embryo’s Mthfr genotype influences its ability to metabolize folates. Here, we explore how the maternal and offspring Mthfr genotypes affect cortical interneuron densities and distributions, mouse social outcome, and the relation of the different interneuron patterns to cortical excitability.

Methods

Two experiments were conducted to examine the effects of maternal and offspring Mthfr-KO heterozygosity. Mice were tested for direct social interactions (DSIs), repetitive behavior and cortical laminar distribution of interneuron populations expressing glutamate-decarboxylase-65, parvalbumin and somatostatin. Susceptibility to seizure was tested by exposure to pentylenetetrazole (PTZ).

Results

Maternal Mthfr+/− genotype was associated with suppressed social activities and reduced interneuron densities in all layers of the retrosplenial cortex (RSC). Somatostatin density and the somatostatin/parvalbumin ratio in the RSC and frontal cortex positively correlated with social behavior in the mice. An interaction between maternal and offspring Mthfr genotypes resulted in higher susceptibility of wild-type offspring to PTZ induced seizure.

Discussion

Maternal folate metabolism was shown to be critical to interneuron ontogenesis. Our results demonstrate that interneurons have a specific susceptibility to folate deficiency that may mediate folate’s involvement in neuropsychiatric disease. The relations between cortical somatostatin interneuron patterns and social behavior highlight this subpopulation of interneurons as a target for further research.
Epitranscriptomic investigation of myopia-associated RNA editing in the retina
Authors: Pan Xu-Bin , He Yu-Shan , Lu Zijing , Pan Hao-Ran , Wei Zhi-Yuan , Jin Yun-Yun , Wang Jihong , Chen Jian-Huan
Published: June 2023

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor (Vldlr) in retinal neovascularization and hypoxia-induced factor 1 alpha (Hif1a). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development.
Bioactive polysaccharides from lotus as potent food supplements: a review of their preparation, structures, biological features and application prospects
Authors: Dai Guona , Wang Jiale , Zheng Jiamei , Xia Conglong , Wang Yaping , Duan Baozhong
Published: June 2023

Lotus is a famous plant of the food and medicine continuum for millennia, which possesses unique nutritional and medicinal values. Polysaccharides are the main bioactive component of lotus and have been widely used as health nutritional supplements and therapeutic agents. However, the industrial production and application of lotus polysaccharides (LPs) are hindered by the lack of a deeper understanding of the structure–activity relationship (SAR), structural modification, applications, and safety of LPs. This review comprehensively comments on the extraction and purification methods and structural characteristics of LPs. The SARs, bioactivities, and mechanisms involved are further evaluated. The potential application and safety issues of LPs are discussed. This review provides valuable updated information and inspires deeper insights for the large scale development and application of LPs.
“DEPHENCE” system—a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer—a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies
Authors: Wilczyński Jacek R. , Wilczyński Miłosz , Paradowska Edyta
Published: June 2023

Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing. Research studies have recently brought some more understanding of the molecular diversity of the ovarian cancer, its unique intraperitoneal biology, the role of cancer stem cells, and the complexity of tumor microenvironment. There is a growing body of evidence that individualization of the treatment adjusted to the molecular and biochemical signature of the tumor as well as to the medical status of the patient should replace or supplement the foregoing therapy. In this review, we have proposed the principles of the novel regimen of the therapy that we called the “DEPHENCE” system, and we have extensively discussed the results of the studies focused on the ovarian cancer stem cells, other components of cancer metastatic niche, and, finally, clinical trials targeting these two environments. Through this, we have tried to present the evolving landscape of treatment options and put flesh on the experimental approach to attack the high-grade serous ovarian cancer multidirectionally, corresponding to the “DEPHENCE” system postulates.
Effect of manual therapy on music students with playing-related musculoskeletal disorders: a prospective study
Authors: Assel Carolin , Nugraha Boya , Kallusky Nicolas , Faßnacht-Lenz Stephan , Altenmüller Eckart , Gutenbrunner Christoph , Sturm Christian
Published: June 2023

Playing Related Musculoskeletal Disorders (PRMD) belong to the most prevalent medical ailments affecting musicians' health and career. This study documents the effect of a physiotherapeutic treatment as well as functional impairments of PRMD on the musculoskeletal system. In total, 32 music students suffering from PRMD were examined in Hanover Medical School (MHH) before and after they received twelve physiotherapeutic treatments, which were carried out over 20 min each over 6 weeks. Additionally, 32 healthy music students, matched by age and gender, were examined at one time point in the MHH to explore which musculoskeletal restrictions are associated with PRMD. The examination included the evaluation of the pain on the Visual Analogue Scale for pain (VAS), a body composition, and body posture measurement, the finger-to-floor distance, the range of motion of the cervical spine, the pressure pain and muscular hypertension examination, the temporomandibular joint-test, the Beighton score screening test, and the testing of the widespread pain score (WSP). After analyzing the data of the patient group (PG) a significant reduction of pain level on the VAS from an average pain of 5.33 to 3.35 was found (large effect). Additionally, a significant reduction of the pressure pain of the M. levator scapulae, the M. rhomboideus, the M. sternocleidomastoideus on the left side and the paravertebral muscles of the cervical spine on the right side after the treatment of the patients could be detected. Regarding the WSP, the positive testing significantly differed, showing a 28% positive testing in the patient group vs. a positive testing of 9% in the control group (CG). As hypermobility is a common phenomenon in musicians, the percentage of those being diagnosed with generalized hypermobility by using the Beighton score in both groups (PG: 37.5%; CG: 25%) was remarkably higher compared to previous studies. In this study, a short course of manual therapy, client tailored for each musician's specific problem, was shown to reduce pain levels in musicians with PRMD.
Magnetic resonance imaging and ultrasound elastography in the context of preclinical pharmacological research: significance for the 3R principles
Authors: Obrecht Michael , Zurbruegg Stefan , Accart Nathalie , Lambert Christian , Doelemeyer Arno , Ledermann Birgit , Beckmann Nicolau
Published: June 2023

The 3Rs principles—reduction, refinement, replacement—are at the core of preclinical research within drug discovery, which still relies to a great extent on the availability of models of disease in animals. Minimizing their distress, reducing their number as well as searching for means to replace them in experimental studies are constant objectives in this area. Due to its non-invasive character in vivo imaging supports these efforts by enabling repeated longitudinal assessments in each animal which serves as its own control, thereby enabling to reduce considerably the animal utilization in the experiments. The repetitive monitoring of pathology progression and the effects of therapy becomes feasible by assessment of quantitative biomarkers. Moreover, imaging has translational prospects by facilitating the comparison of studies performed in small rodents and humans. Also, learnings from the clinic may be potentially back-translated to preclinical settings and therefore contribute to refining animal investigations. By concentrating on activities around the application of magnetic resonance imaging (MRI) and ultrasound elastography to small rodent models of disease, we aim to illustrate how in vivo imaging contributes primarily to reduction and refinement in the context of pharmacological research.
Functional roles of two novel P450 genes in the adaptability of Conogethes punctiferalis to three commonly used pesticides
Authors: Yuan Xingxing , Li Han , Guo Xianru , Jiang He , Zhang Qi , Zhang Lijuan , Wang Gaoping , Li Weizheng , Zhao Man
Published: June 2023

Introduction: Insect cytochrome P450 (CYP450) genes play important roles in the detoxification and metabolism of xenobiotics, such as plant allelochemicals, mycotoxins and pesticides. The polyphagous Conogethes punctiferalis is a serious economic pest of fruit trees and agricultural crops, and it shows high adaptability to different living environments.

Methods: The two novel P450 genes CYP6CV1 and CYP6AB51 were identified and characterized. Quantitative real-time PCR (qRT-PCR) technology was used to study the expression patterns of the two target genes in different larval developmental stages and tissues of C. punctiferalis. Furthermore, RNA interference (RNAi) technology was used to study the potential functions of the two P450 genes by treating RNAi-silenced larvae with three commonly used pesticides.

Results: The CYP6CV1 and CYP6AB51 genes were expressed throughout various C. punctiferalis larval stages and in different tissues. Their expression levels increased along with larval development, and expression levels of the two target genes in the midgut were significantly higher than in other tissues. The toxicity bioassay results showed that the LC50 values of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin on C. punctiferalis larvae were 0.2028 μg/g, 0.0683 μg/g and 0.6110 mg/L, respectively. After treating with different concentrations of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin (LC10, LC30, LC50), independently, the relative expressions of the two genes CYP6CV1 and CYP6AB51 were significantly induced. After the dsRNA injection, the expression profiles of the two CYP genes were reduced 72.91% and 70.94%, respectively, and the mortality rates of the larvae significantly increased when treated with the three insecticides independently at LC10 values.

Discussion: In the summary, after interfering with the CYP6CV1 and CYP6AB51 in C. punctiferalis, respectively, the sensitivity of C. punctiferalis to chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin was significantly increased, indicating that the two CYP6 genes were responsible for the adaptability of C. punctiferalis to the three chemical insecticides in C. punctiferalis. The results from this study demonstrated that CYP6CV1 and CYP6AB51 in C. punctiferalis play crucial roles in the detoxification of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin.
Geographical equations of Swertia mussotii bioactivities: evidence from the western Sichuan region of China
Authors: Wang Xiaobo , Shen Cheng , Chen Tao , Zhou Xiaodan , Li Yulin
Published: June 2023

Swertia mussotii is the most authentic raw material used in Tibetan medicine in China for its various bioactivities. This natural medicine resource is at risk of being exhausted due to the double interference of climate change and anthropogenic over-collection. Little is known about habitat characteristics and the crucial environmental factors that influence the levels of active ingredients. The goal of this study is to understand the variability in the bioactive compound content of a wide range of wild S. mussotii as it adapts to changing environmental conditions. The target compound content of the whole plant material was analyzed with the environmental explanatory variables of the field sample sites using a constrained ordination method for their correlation analysis. The results show that 16.3 percent of the sampled wild S. mussotii populations with the highest bioactive content can be grouped into the elite type. The most prominent environmental variables affecting the content of major bioactive products include altitude, aspect, soil TK content, Fe content, and C/N and N/P ratios. Altitude and aspect put indirect effects that are mediated by plant height and density, N/P ratio puts a direct effect, while soil TK content, Fe content and C/N ratio have both direct and indirect effects on the bioactivity of S. mussotii. In addition to the total negative effects of altitude and C/N ratio, the remaining factors play a driving role. These findings demonstrate variation by geographical conditions across S. mussotii accessions for physiologic responses and secondary compounds in wild populations. The knowledge gained from this study can be used for environmental and plant physiology research, efficient collection of naturally active compounds, and conservation strategies for rare natural plant resources.
Discovering compassion in medical training: a qualitative study with curriculum leaders, educators, and learners
Authors: Lane Charles B. , Brauer Erin , Mascaro Jennifer S.
Published: June 2023

Background

Compassion is considered a fundamental human capacity instrumental to the creation of medicine and for patient-centered practice and innovations in healthcare. However, instead of nurturing and cultivating institutional compassion, many healthcare providers cite the health system itself as a direct barrier to standard care. The trend of compassion depletion begins with medical students and is often attributed to the culture of undergraduate medical training, where students experience an increased risk of depression, substance use, and suicidality.

Objectives

This qualitative study aims to develop a more comprehensive understanding of compassion as it relates to undergraduate medical education. We used focus groups with key stakeholders in medical education to characterize beliefs about the nature of compassion and to identify perceived barriers and facilitators to compassion within their daily responsibilities as educators and students.

Methods

Researchers conducted a series of virtual (Zoom) focus groups with stakeholders: Students (N = 14), Small Group Advisors (N = 11), and Medical Curriculum Leaders (N = 4). Transcripts were thematically analyzed using MAXQDA software.

Results

Study participants described compassion as being more than empathy, demanding action, and capable of being cultivated. Stakeholders identified self-care, life experiences, and role models as facilitators. The consistently identified barriers to compassion were time constraints, culture, and burnout. Both medical students and those training them agreed on a general definition of compassion and that there are ways to cultivate more of it in their daily professional lives. They also agreed that undergraduate medical education – and the healthcare culture at large – does not deliberately foster compassion and may be directly contributing to its degradation by the content and pedagogies emphasized, the high rates of burnout and futility, and the overwhelming time constraints.

Discussion

Intentional instruction in and cultivation of compassion during undergraduate medical education could provide a critical first step for undergirding the professional culture of healthcare with more resilience and warm-hearted concern. Our finding that medical students and those training them agree about what compassion is and that there are specific and actionable ways to cultivate more of it in their professional lives highlights key changes that will promote a more compassionate training environment conducive to the experience and expression of compassion.
Right inferior frontal gyrus theta-burst stimulation reduces smoking behaviors and strengthens fronto-striatal-limbic resting-state functional connectivity: a randomized crossover trial
Authors: Upton Spencer , Brown Alexander A. , Golzy Mojgan , Garland Eric L. , Froeliger Brett
Published: June 2023

Introduction

Functional and anatomical irregularities in the right inferior frontal gyrus (rIFG), a ventrolateral prefrontal region that mediates top-down inhibitory control over prepotent behavioral responding, are implicated in the ongoing maintenance of nicotine dependence (ND). However, there is little research on the effects of neuromodulation of the rIFG on smoking behavior, inhibitory control, and resting-state functional connectivity (rsFC) among individuals with ND.

Methods

In this double-blind, crossover, theta-burst stimulation (TBS) study, adults with ND (N = 31; female: n = 15) completed a baseline session and were then randomized to two counterbalanced sessions of functionally neuronavigated TBS to the rIFG: continuous TBS (cTBS) on 1 day and intermittent TBS (iTBS) on another. Differences in cigarette cravings, smoking, and fronto-striatal-limbic rsFC were assessed.

Results

Relative to baseline, cTBS significantly reduced appetitive and withdrawal cravings immediately after treatment. The effects of cTBS on withdrawal craving persisted for 24 h, as well as produced a reduction in smoking. Furthermore, cTBS significantly strengthened rsFC between the rIFG pars opercularis and subcallosal cingulate (fronto-striatal circuit), and between the rIFG pars opercularis and the right posterior parahippocampal gyrus (fronto-limbic circuit). At post-24 h, cTBS-induced increase in fronto-striatal rsFC was significantly associated with less appetitive craving, while the increase in fronto-limbic rsFC was significantly associated with less withdrawal craving and smoking.

Discussion

These findings warrant further investigation into the potential value of rIFG cTBS to attenuate smoking behavior among individuals with ND.
Binocular rivalry in autistic and socially anxious adults
Authors: Kamhout Sarah , Olivier Joshua M. , Morris Jarom , Brimhall Hayden R. , Black Braeden L. , Gabrielsen Terisa P. , South Mikle , Lundwall Rebecca A. , Nielsen Jared A.
Published: June 2023

Background

Social anxiousness is a pervasive symptom in both social anxiety disorder and autism spectrum conditions. Binocular rivalry, which occurs when different images are presented to each eye, has been used to explore how visual and cognitive processing differs across various clinical diagnoses. Previous studies have separately explored whether individuals with autism or anxiety experience binocular rivalry in ways that are different from neurotypical individuals.

Methods

We applied rivalry paradigms that are similar to those used in previous studies of autism and general anxiety to individuals experiencing symptoms of social anxiousness at clinical or subclinical levels. We also incorporated rivalrous stimuli featuring neutral and emotional facial valances to explore potential overlap of social processing components in social anxiety and autism.

Results

We hypothesized that higher levels of social anxiousness would increase binocular rivalry switch rates and that higher levels of autistic traits would decrease switch rates. However, stimulus condition did not affect switch rates in either diagnostic group, and switch rate was not significantly predictive of dimensional measures of either autism or social anxiety.

Discussion

This may suggest a common mechanism for atypical visual cognition styles previously associated with social anxiety and autism. Alternatively, differences in switch rates may only emerge at higher trait levels than reported by the participants in our studies. Furthermore, these findings may be influenced by sex differences in our unique sample.
White matter microstructural perturbations after total sleep deprivation in depression
Authors: Taraku Brandon , Zavaliangos-Petropulu Artemis , Loureiro Joana R. , Al-Sharif Noor B. , Kubicki Antoni , Joshi Shantanu H. , Woods Roger P. , Espinoza Randall , Narr Katherine L. , Sahib Ashish K.
Published: June 2023

Background

Total sleep deprivation (TSD) transiently reverses depressive symptoms in a majority of patients with depression. How TSD modulates diffusion tensor imaging (DTI) measures of white matter (WM) microstructure, which may be linked with TSD’s rapid antidepressant effects, remains uncharacterized.

Methods

Patients with depression (N = 48, mean age = 33, 26 women) completed diffusion-weighted imaging and Hamilton Depression Rating (HDRS) and rumination scales before and after >24 h of TSD. Healthy controls (HC) (N = 53, 23 women) completed the same assessments at baseline, and after receiving TSD in a subset of HCs (N = 15). Tract based spatial statistics (TBSS) investigated voxelwise changes in fractional anisotropy (FA) across major WM pathways pre-to-post TSD in patients and HCs and between patients and HCs at baseline. Post hoc analyses tested for TSD effects for other diffusion metrics, and the relationships between change in diffusion measures with change in mood and rumination symptoms.

Results

Significant improvements in mood and rumination occurred in patients with depression (both p < 0.001), but not in HCs following TSD. Patients showed significant (p < 0.05, corrected) decreases in FA values in multiple WM tracts, including the body of the corpus callosum and anterior corona radiata post-TSD. Significant voxel-level changes in FA were not observed in HCs who received TSD (p > 0.05). However, differential effects of TSD between HCs and patients were found in the superior corona radiata, frontal WM and the posterior thalamic radiation (p < 0.05, corrected). A significant (p < 0.05) association between change in FA and axial diffusivity within the right superior corona radiata and improvement in rumination was found post-TSD in patients.

Conclusion

Total sleep deprivation leads to rapid microstructural changes in WM pathways in patients with depression that are distinct from WM changes associated with TSD observed in HCs. WM tracts including the superior corona radiata and posterior thalamic radiation could be potential biomarkers of the rapid therapeutic effects of TSD. Changes in superior corona radiata FA, in particular, may relate to improvements in maladaptive rumination.
Mapping the disparities in intimate partner violence prevalence and determinants across Sub-Saharan Africa
Authors: Mossie Tilahun B. , Mekonnen Fenta Haile , Tadesse Meseret , Tadele Animut
Published: June 2023

Objective

This study aimed to map disparities in prevalence and associated factors across countries in Sub-Saharan Africa.

Methods

We used National Demographic and Health Survey (DHS) data from 26 countries in the region with 114,340 participants. Women and girls in the reproductive age group of 15 to 49 years were included in the study. To map disparities across countries and their provinces, we employed the kriging interpolation technique. We used STATA for data management.

Result

The prevalence of physical, emotional and sexual IPV in Sub-Saharan Africa was 30.58, 30.22, and 12.6% respectively, and at least one form of IPV was 42.62%. Disparities were observed across the countries and provinces in each country. Younger age, secondary-level education and above, moderate participation in decision-making, not working out of home, not afraid of the spouse, rich (wealth index), not having a child, high maternal literacy, and rural residence relatively decreased the odds of IPV. The husbands’ lower education, alcohol consumption, and high controlling behavior increased the probability of IPV.

Conclusion

The prevalence of Intimate Partner Violence in Sub-Saharan Africa is the highest in the world, a signal that the global agenda to end all forms of violence against women will be difficult to achieve. There is a large gap across countries and provinces in each country. Area-specific intervention packages that focus on modifiable factors should be strengthened.
Head-mounted augmented reality to support reassurance and social interaction for autistic children with severe learning disabilities
Authors: Bauer Valentin , Bouchara Tifanie , Duris Olivier , Labossière Charlotte , Clément Marie-Noëlle , Bourdot Patrick
Published: June 2023

Augmented Reality (AR) is promising to complement autism approaches, but so far has mainly focused on training socio-emotional abilities for autistic children with mild learning disabilities. To better consider autistic children with severe learning disabilities and complex needs (SLN), stakeholders advise using collaborative AR sensory-based mediation approaches. Magic Bubbles is a multisensory AR environment created based on stakeholders’ interviews, then adapted for a day hospital setting in collaboration with practitioners, and finally validated in terms of acceptability and usability for autistic children with SLN. In this paper, we report on our latest study that explores three main research questions: 1) To what extent can Magic Bubbles secure autistic children with SLN? 2) To what extent can Magic Bubbles prompt the dyadic relationship between an autistic child with SLN and a practitioner? 3) What is the overall quality of experience for autistic children with SLN when using Magic Bubbles? To answer these questions, seven autistic children with SLN participated in at least six weekly sessions over three months in a day hospital setting. Data collection and analysis used qualitative and quantitative methods, mainly drawing upon grounded theory to evaluate their experiences. Findings validate the three research questions, offer a detailed account of children’s experiences with AR, and outline future directions.
Governance and trust in sustainability-based agri-food value chains. A comparative analysis of five cases in Germany
Authors: Grohmann Pascal , Dietze Victoria , Krämer Christine , Feindt Peter H.
Published: June 2023

Value chains that generate an increased willingness to pay among consumers by offering enhanced levels of sustainability are widely discussed as an important strategy for creating new business opportunities and fostering food system transformation. Previous research has highlighted the importance of governance arrangements to secure the trust necessary for the establishment of sustainability-based value chains. However, how different coordination designs by private and public actors along the value chain affect trust formation is not well understood. To address this question, this paper combines the concepts of hybrid governance and multidimensional trust to guide a comparative analysis of five sustainability-based agri-food value chains in Germany as exemplary case studies. The findings show that different types of governance activities are necessary to build the capacity to address four different sources of trust: dispositional, affinitive, rational and procedural trust. Building trust capacities facilitates coordination of activities along the value chain and reliable delivery of sustainability-related value propositions. In all five cases, governance arrangements and building of trust capacities were geared towards increasing willingness to pay. Sustainability-based agri-food value chains have therefore limited potential to internalize the agri-food sector’s substantial negative externalities.
Effect of different rice planting methods on the water, energy and carbon footprints of subsequent wheat
Authors: Jin Zhaoqiang , Mu Yixue , Li Yusheng , Nie Lixiao
Published: June 2023

The rice-wheat rotation system is an important planting system in the middle and lower reaches of the Yangtze River. Studies on the effects of different rice planting methods on the water, energy, and carbon footprints of subsequent wheat have rarely been reported. In this study, the effects of different rice cultivation practices on the water, energy, and carbon footprints of subsequent wheat were investigated among different rice-wheat rotation systems including dry direct-seeded rice (DSR)-wheat rotation, wet direct-seeded rice (WSR)-wheat rotation and transplanted rice(TPR)-wheat rotation. Results showed that the yield of wheat after DSR was 8,552 kg ha−1, which was 14.61 and 4.72% higher than the yields after WSR and TPR, respectively. In addition, the water and carbon footprints of wheat after DSR were lower than those after WSR and TPR, while its energy and carbon production efficiencies and net ecosystem economic benefits were higher than those after WSR and TPR. Notably, the use of fertilizers and fuel are the two major contributors to the high energy inputs and greenhouse gas emissions in wheat production. In summary, wheat after DSR has higher ecological and economic benefits, and we recommend that it be promoted as the preferred wheat planting model in rice-wheat rotation areas.
Therapeutic Drug Monitoring of Mycophenolic Acid Identifies Kidney Transplant Recipients Responsive to Two SARS-CoV-2 mRNA Vaccine Doses
Authors: von Moos Seraina , Rho Elena , Dammann Maria , Kokkonen Sanna Marjaana , Mueller Thomas F. , Schachtner Thomas
Published: June 2023

Immune-responsiveness to SARS-CoV-2 mRNA vaccination is reduced in kidney transplant recipients (KTRs). Previous reports point to a role of mycophenolic acid (MPA). Our observational cohort study included all KTRs at University Hospital Zurich receiving two SARS-CoV-2 mRNA vaccine doses more than 6 months post-transplantation, who were assessed by measuring anti-spike immunoglobulin G (IgG). We applied principles of therapeutic drug monitoring (TDM) to correlate MPA exposure and lymphocyte counts with SARS-CoV-2 IgG. MPA trough levels differ largely among KTRs with a median of 3.1 mg/L (range 0.7–9.5 mg/L). 34 of 84 KTRs (40%) developed positive SARS-CoV-2 IgG after two vaccine doses. KTRs who developed positive SARS-CoV-2 IgG showed significantly higher eGFR (p < 0.001), lower MPA trough levels (p < 0.001) and higher CD19+ lymphocytes (p < 0.001). MPA trough levels <2.5 mg/l and CD19+ lymphocytes >40/μl identify KTRs with seroconversion. Upon logistic regression, MPA trough levels <2.5 mg/L were associated with a 7-fold (CI 95%: 1.589–29.934) and ciclosporin use with a 6-fold (CI 95%: 1.148–30.853) increase in the odds of seroconversion. Our study indicates that immune-responsiveness to SARS-CoV-2 mRNA vaccines correlates with MPA exposure measured by MPA trough level but argues against a class effect of MPA. TDM-guided MPA dosing may be a strategy to increase seroconversion rate.