bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal patterns of endophytic microbial heterogeneity across distinct ecological compartments within the Panax ginseng root system following deforestation for cultivation
Authors: Shi Zhenting , Yang Limin , Yang Meiling , Li Kexin , Yang Li , Han Mei
Published: May 2024

Alterations in the microbial community significantly impact the yield and quality of ginseng. Yet, the dynamics of microbial community shifts within the root endophytes of ginseng across varying cultivation periods remain inadequately understood. This study zeroes in on the microbial community variations within the xylem (M), phloem (R), and fibrous roots (X) of ginseng during the fourth (F4) and fifth (F5) years of cultivation, aiming to bridge this research gap. We assessed soil physicochemical properties, enzyme activities, and nine individual saponins, complemented by high-throughput sequencing techniques (16S rDNA and ITS) to determine their profiles. The results showed that cultivation years mainly affected the microbial diversity of endophytic bacteria in ginseng fibrous roots compartment: the ASVs number and α-diversity Chao1 index of bacteria and fungi in F5X compartment with higher cultivation years were significantly higher than those in F4X compartment with lower cultivation years. It is speculated that the changes of fibrous roots bacterial groups may be related to the regulation of amino acid metabolic pathway. Such as D-glutamine and D-glutamate metabolism D-glutamine, cysteine and methionine metabolism regulation. The dominant bacteria in ginseng root are Proteobacteria (relative abundance 52.07–80.35%), Cyanobacteria (1.97–42.52%) and Bacteroidota (1.11–5.08%). Firmicutes (1.28–3.76%). There were two dominant phyla: Ascomycota (60.10–93.71%) and Basidiomycota (2.25–30.57%). Endophytic fungi were more closely related to soil physicochemical properties and enzyme activities. AN, TK, OP, SWC and EC were the main driving factors of endophytic flora of ginseng root. Tetracladium decreased with the increase of cultivation years, and the decrease was more significant in phloem (F4R: 33.36%, F5R: 16.48%). The relative abundance of Bradyrhizobium, Agrobacterium and Bacillus in each ecological niche increased with the increase of cultivation years. The relative abundance of Bradyrhizobium and Agrobacterium in F5X increased by 8.35 and 9.29 times, respectively, and Bacillus in F5M increased by 5.57 times. We found a variety of potential beneficial bacteria and pathogen antagonists related to ginseng biomass and saponins, such as Bradyrhizobium, Agrobacterium, Bacillus and Exophiala, which have good potential for practical application and development.
The effect of selenium supplementation on oxidative stress, clinical and physiological symptoms in patients with migraine: a double-blinded randomized clinical trial
Authors: Balali Arghavan , Sadeghi Omid , Khorvash Fariborz , Rouhani Mohammad Hossein , Askari Gholamreza
Published: May 2024

Background and Aim

The present double-blinded randomized clinical trial aimed to investigate the effect of selenium supplementation on oxidative stress, clinical, and physiological symptoms in patients with migraine.

Methods

In total, 72 patients with migraine were randomly assigned to receive either 200 μg/day selenium (n = 36) or placebo (n = 36) for 12 weeks. Clinical traits of migraine (e.g., severity, frequency, and duration of headaches), mental health indices (e.g., depression, anxiety, and distress), quality of life, biomarkers of oxidative stress (e.g., nitric oxide [NO], malondialdehyde [MDA], total antioxidant capacity [TAC], total oxidant status [TOS]), and anthropometric indices were assessed at baseline and at the end of the study.

Results

Selenium supplementation resulted in a significant reduction in NO (−1.24 ± 0.43 vs. 0.16 ± 0.43; p = 0.03) levels and a significant increase in TAC (9.89 ± 2.50 vs. −0.18 ± 2.50; p = 0.01) compared to the placebo group. Moreover, selenium supplementation had a significant protective effect against MDA levels compared to placebo (0.33 ± 0.57 vs. 1.83 ± 0.57; p = 0.03). In addition, selenium intake was associated with a lower headache frequency (−8.15 ± 0.77 vs. −4.12 ± 0.77; p < 0.001) and severity (−2.89 ± 0.42 vs. −1.16 ± 0.42; p = 0.01) as well as a lower Headache Impact Test-6 (HIT-6) score (−9.22 ± 2.00 vs. −2.08 ± 2.00; p = 0.02) compared to the controls. For other outcome variables, we found no significant effect.

Conclusion

Selenium supplement may be considered a complementary therapy in patients with migraine due to its beneficial effects on oxidative stress and migraine symptoms. Further studies are needed to affirm our findings.

Clinical Trial Registration: This study was registered in the Iranian Registry of Clinical Trials (https://www.irct.ir) on 27 May 2023 with code number of IRCT20121216011763N60.
KDM7A-DT induces genotoxic stress, tumorigenesis, and progression of p53 missense mutation-associated invasive breast cancer
Authors: Giannakakis Antonis , Tsifintaris Margaritis , Gouzouasis Vasileios , Ow Ghim Siong , Aau Mei Yee , Papp Csaba , Ivshina Anna V. , Kuznetsov Vladimir A.
Published: May 2024

Stress-induced promoter-associated and antisense lncRNAs (si-paancRNAs) originate from a reservoir of oxidative stress (OS)-specific promoters via RNAPII pausing-mediated divergent antisense transcription. Several studies have shown that the KDM7A divergent transcript gene (KDM7A-DT), which encodes a si-paancRNA, is overexpressed in some cancer types. However, the mechanisms of this overexpression and its corresponding roles in oncogenesis and cancer progression are poorly understood. We found that KDM7A-DT expression is correlated with highly aggressive cancer types and specific inherently determined subtypes (such as ductal invasive breast carcinoma (BRCA) basal subtype). Its regulation is determined by missense TP53 mutations in a subtype-specific context. KDM7A-DT transcribes several intermediate-sized ncRNAs and a full-length transcript, exhibiting distinct expression and localization patterns. Overexpression of KDM7A-DT upregulates TP53 protein expression and H2AX phosphorylation in nonmalignant fibroblasts, while in semi-transformed fibroblasts, OS superinduces KDM7A-DT expression in a TP53-dependent manner. KDM7A-DT knockdown and gene expression profiling in TP53-missense mutated luminal A BRCA variant, where it is abundantly expressed, indicate its significant role in cancer pathways. Endogenous over-expression of KDM7A-DT inhibits DNA damage response/repair (DDR/R) via the TP53BP1-mediated pathway, reducing apoptosis and promoting G2/M checkpoint arrest. Higher KDM7A-DT expression in BRCA is associated with KDM7A-DT locus gain/amplification, higher histologic grade, aneuploidy, hypoxia, immune modulation scores, and activation of the c-myc pathway. Higher KDM7A-DT expression is associated with relatively poor survival outcomes in patients with luminal A or Basal subtypes. In contrast, it is associated with favorable outcomes in patients with HER2+ER- or luminal B subtypes. KDM7A-DT levels are coregulated with critical transcripts and proteins aberrantly expressed in BRCA, including those involved in DNA repair via non-homologous end joining and epithelial-to-mesenchymal transition pathway. In summary, KDM7A-DT and its si-lncRNA exhibit several intrinsic biological and clinical characteristics that suggest important roles in invasive BRCA and its subtypes. KDM7A-DT-defined mRNA and protein subnetworks offer resources for identifying clinically relevant RNA-based signatures and prospective targets for therapeutic intervention.
Chronic kidney disease with malignant peripheral nerve sheath tumor of the ureter: a case report
Authors: Yin Xinyang , Wang Xiaodong , He Zhenlin , Chen Xiaolong , Wang Qing , Jiang Kehua
Published: May 2024

Malignant peripheral nerve sheath tumors (MPNSTs) are a complex group of malignant tumors originating from nerve cells or benign peripheral nerve sheath tumors and are commonly found in major plexus/nerve root sites such as the limbs, head, and neck. Malignant peripheral nerve sheath tumors originating in the ureter are extremely rare. Herein, we report the case of a 63-year-old patient with a malignant peripheral nerve sheath tumor of the right ureter who underwent laparoscopic radical resection of the right kidney and ureter. The patient also had stage 5 chronic kidney disease (CKD). Therefore, chemotherapy and radiotherapy were not considered. No tumor recurrence was observed during the follow-up period.
Phosphorylation of cell cycle and apoptosis regulatory protein-1 by stress activated protein kinase P38γ is a novel mechanism of apoptosis signaling by genotoxic chemotherapy
Authors: Venkatesh Jaganathan , Muthu Magesh , Singaravelu Indulekha , Cheriyan Vino T. , Sekhar Sreeja C. , Acharige Nuwan C. P. N. , Levi Edi , Assad Hadeel , Pflum Mary Kay H. , Rishi Arun K.
Published: May 2024

CARP-1, a perinuclear phospho-protein, regulates cell survival and apoptosis signaling induced by genotoxic drugs. However, kinase(s) phosphorylating CARP-1 and down-stream signal transduction events remain unclear. Here we find that CARP-1 Serine (S)626 and Threonine (T)627 substitution to Alanines (AA) inhibits genotoxic drug-induced apoptosis. CARP-1 T627 is followed by a Proline (P), and this TP motif is conserved in vertebrates. Based on these findings, we generated affinity-purified, anti-phospho-CARP-1 T627 rabbit polyclonal antibodies, and utilized them to elucidate chemotherapy-activated, CARP-1-dependent cell growth signaling mechanisms. Our kinase profiling studies revealed that MAPKs/SAPKs phosphorylated CARP-1 T627. We then UV cross-linked protein extracts from Adriamycin-treated HeLa cervical cancer cells with a CARP-1 (614–638) peptide, and conducted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the peptide-bound protein complexes. This experiment revealed SAPK p38γ interaction with CARP-1 (614–638) peptide. Our studies further established that SAPK p38γ, but not other MAPKs, phosphorylates CARP-1 T627 in cancer cells treated with genotoxic drugs. Loss of p38γ abrogates CARP-1 T627 phosphorylation, and results in enhanced survival of breast cancer cells by genotoxic drugs. CARP-1 T627 phosphorylation was also noted in breast tumors from patients treated with radiation or endocrine therapies. We conclude that genotoxic drugs activate p38γ-dependent CARP-1 T627 phosphorylation to inhibit cell growth.
The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis
Authors: Zhao Pengfei , Zhao Ting , Yu Lihong , Ma Wenming , Liu Wenyu , Zhang Chenning
Published: May 2024

Objective

Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors.

Methods

We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303).

Results

A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism.

Conclusion

Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians.

Systematic review registration

crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).
The deregulation of arachidonic acid metabolism in ovarian cancer
Authors: Xia Qiuyi , Gao Wen , Yang Jintao , Xing Zhifang , Ji Zhaodong
Published: May 2024

Arachidonic acid (AA) is a crucial polyunsaturated fatty acid in the human body, metabolized through the pathways of COX, LOX, and cytochrome P450 oxidase to generate various metabolites. Recent studies have indicated that AA and its metabolites play significant regulatory roles in the onset and progression of ovarian cancer. This article examines the recent research advancements on the correlation between AA metabolites and ovarian cancer, both domestically and internationally, suggesting their potential use as biological markers for early diagnosis, targeted therapy, and prognosis monitoring.
Trend analysis and age-period-cohort effects on morbidity and mortality of liver cancer from 2010 to 2020 in Guangzhou, China
Authors: Wang Dedong , Hu Xiangzhi , Xu Huan , Chen Yuanyuan , Wang Suixiang , Lin Guozhen , Yang Lei , Chen Jinbin , Zhang Lin , Qin Pengzhe , Wu Di , Liang Boheng
Published: May 2024

Introduction

Liver cancer is one of the most common malignant gastrointestinal tumors worldwide. This study intends to provide insight into the epidemiological characteristics and development trends of liver cancer incidence and mortality from 2010 to 2020 in Guangzhou, China.

Methods

Data were collected from the Cancer Registry and Reporting Office of Guangzhou Center for Disease Control and Prevention. Cross-sectional study, Joinpoint regression (JPR) model, and Age-Period-Cohort (APC) model were conducted to analyze the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) trend of liver cancer among the entire study period.

Results

The age-standardized incidence and mortality of liver cancer in Guangzhou showed an overall decreasing trend. The disparity in risk of morbidity and mortality between the two sexes for liver cancer is increasing. The cohort effect was the most significant among those born in 1965~1969, and the risk of liver cancer incidence and mortality in the total population increased and then decreased with the birth cohort. Compared with the birth cohort born in 1950~1954 (the reference cohort), the risk of liver cancer incidence and mortality in the males born in 1995~1999 decreased by 32% and 41%, respectively, while the risk in the females decreased by 31% and 32%, respectively.

Conclusions

The early detection, prevention, clinical diagnosis, and treatment of liver cancer in Guangzhou have made remarkable achievements in recent years. However, the risk of liver cancer in the elderly and the middle-aged males is still at a high level. Therefore, the publicity of knowledge related to the prevention and treatment of liver cancer among the relevant population groups should be actively carried out to enhance the rate of early diagnosis and treatment of liver cancer and to advocate a healthier lifestyle.
Physiologically based pharmacokinetic modeling to predict the pharmacokinetics of codeine in different CYP2D6 phenotypes
Authors: Yang Yujie , Zhang Xiqian , Wang Yirong , Xi Heng , Xu Min , Zheng Liang
Published: May 2024

Objectives

Codeine, a prodrug used as an opioid agonist, is metabolized to the active product morphine by CYP2D6. This study aimed to establish physiologically based pharmacokinetic (PBPK) models of codeine and morphine and explore the influence of CYP2D6 genetic polymorphisms on the pharmacokinetics of codeine and morphine.

Methods

An initial PBPK modeling of codeine in healthy adults was established using PK-Sim® software and subsequently extrapolated to CYP2D6 phenotype-related PBPK modeling based on the turnover frequency (Kcat) of CYP2D6 for different phenotype populations (UM, EM, IM, and PM). The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between the predicted and observed values of the pharmacokinetic parameters to evaluate the accuracy of PBPK modeling. The validated models were then used to support dose safety for different CYP2D6 phenotypes.

Results

The developed and validated CYP2D6 phenotype-related PBPK model successfully predicted codeine and morphine dispositions in different CYP2D6 phenotypes. Compared with EMs, the predicted AUC0-∞ value of morphine was 98.6% lower in PMs, 60.84% lower in IMs, and 73.43% higher in UMs. Morphine plasma exposure in IMs administered 80 mg of codeine was roughly comparable to that in EMs administered 30 mg of codeine. CYP2D6 UMs may start dose titration to achieve an optimal individual regimen and avoid a single dose of over 20 mg. Codeine should not be used in PMs for pain relief, considering its insufficient efficacy.

Conclusion

PBPK modeling can be applied to explore the dosing safety of codeine and can be helpful in predicting the effect of CYP2D6 genetic polymorphisms on drug–drug interactions (DDIs) with codeine in the future.
Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology
Authors: Echeverría-Garcés Gabriela , Ramos-Medina María José , Vargas Rodrigo , Cabrera-Andrade Alejandro , Altamirano-Colina Adriana , Freire María Paula , Montalvo-Guerrero Juliana , Rivera-Orellana Sebastián , Echeverría-Espinoza Paulina , Quiñones Luis A. , López-Cortés Andrés
Published: May 2024

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential.

Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data.

Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins.

Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.
Multidrug resistance transporters P-gp and BCRP limit the efficacy of ATR inhibitor ceralasertib in cancer cells
Authors: Chen Xuan-Yu , Wu Zhuo-Xun , Wang Jing-Quan , Teng Qiu-Xu , Tang Hailin , Liu Qianwen , Chen Zhe-Sheng , Chen Wenkuan
Published: May 2024

The therapeutic effect of chemotherapy and targeted therapy are known to be limited by drug resistance. Substantial evidence has shown that ATP-binding cassette (ABC) transporters P-gp and BCRP are significant contributors to multidrug resistance (MDR) in cancer cells. In this study, we demonstrated that a clinical-staged ATR inhibitor ceralasertib is susceptible to P-gp and BCRP-mediated MDR. The drug resistant cancer cells were less sensitive to ceralasertib compared to the parental cells. Moreover, ceralasertib resistance can be reversed by inhibiting the drug efflux activity of P-gp and BCRP. Interestingly, ceralasertib was able to downregulate the level of P-gp but not BCRP, suggesting a potential regulation between ATR signaling and P-gp expression. Furthermore, computational docking analysis predicted high affinities between ceralasertib and the drug-binding sites of P-gp and BCRP. In summary, overexpression of P-gp and BCRP are sufficient to confer cancer cells resistance to ceralasertib, underscoring their role as biomarkers for therapeutic efficacy.
Thyroid disorders and gastrointestinal dysmotility: an old association
Authors: Xu Guang-Meng , Hu Ming-Xin , Li Si-Yu , Ran Xuan , Zhang Hao , Ding Xiang-Fu
Published: May 2024

Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of the symptoms may vary. The exact mechanism of action of thyroid hormones on gastrointestinal motility is not completely understood, however, a clue lies in the fact that muscle cell receptors can be directly acted upon by thyroxines. Both hypo- and hyperthyroidism can cause impairment of gastrointestinal motility, modifying structure and function of pharynx and esophagus, and regulating esophageal peristalsis through neuro-humoral interaction. In hyperthyroid patients, alterations of postprandial and basic electric rhythms have been observed at gastro-duodenal level, often resulting in slower gastric emptying. Gastric emptying may also be delayed in hypothyroidism, but an unrelated gastric mucosa-affecting chronic modification may also cause such pattern. Hyperthyroidism commonly show malabsorption and diarrhoea, while hypothyroidism frequently show constipation. In summary, it can be stated that symptoms of gastrointestinal motility dysfunction can be related to thyroid diseases, affecting any of the gastrointestinal segment. Clinically, the typical thyroid disease manifestations may be missing, borderline, or concealed because of intercurrent sicknesses. Motility-linked gastrointestinal problems may easily conceal a misdetected, underlying dysthyroidism that should be carefully analyzed. Here, we aim to elaborate on the associations between thyroid disorders and GI dysmotility and the common clinical manifestations associated with GI dysmotility.
The influence of social feedback on reward learning in the Iowa gambling task
Authors: Peng Ming , Duan Qiaochu , Yang Xiaoying , Tang Rui , Zhang Lei , Zhang Hanshu , Li Xu
Published: May 2024

Learning, an important activity for both human and animals, has long been a focal point of research. During the learning process, subjects assimilate not only their own information but also information from others, a phenomenon known as social learning. While numerous studies have explored the impact of social feedback as a reward/punishment during learning, few studies have investigated whether social feedback facilitates or inhibits the learning of environmental rewards/punishments. This study aims to test the effects of social feedback on economic feedback and its cognitive processes by using the Iowa Gambling Task (IGT). One hundred ninety-two participants were recruited and categorized into one non-social feedback group and four social feedback groups. Participants in the social feedback groups were informed that after the outcome of each choice, they would also receive feedback from an online peer. This peer was a fictitious entity, with variations in identity (novice or expert) and feedback type (random or effective). The Outcome-Representation Learning model (ORL model) was used to quantify the cognitive components of learning. Behavioral results showed that both the identity of the peer and the type of feedback provided significantly influenced the deck selection, with effective social feedback increasing the ratio of chosen good decks. Results in the ORL model showed that the four social feedback groups exhibited lower learning rates for gain and loss compared to the nonsocial feedback group, which suggested, in the social feedback groups, the impact of the recent outcome on the update of value decreased. Parameters such as forgetfulness, win frequency, and deck perseverance in the expert-effective feedback group were significantly higher than those in the non-social feedback and expert-random feedback groups. These findings suggest that individuals proactively evaluate feedback providers and selectively adopt effective feedback to enhance learning.
Laughter in everyday life: an event-based experience sampling method study using wrist-worn wearables
Authors: Stieger Stefan , Volsa Selina , Willinger David , Lewetz David , Batinic Bernad
Published: May 2024

Laughter is a universal, nonverbal vocal expression of broad significance for humans. Interestingly, rather little is known about how often we laugh and how laughter is associated with our personality. In a large, event-based, experience sampling method study (N = 52; k = 9,261 assessments) using wrist-worn wearables and a physical analogue scale, we analyzed belly laughs and fit of laughter events in participants’ everyday life for 4 weeks. Additionally, we assessed associations with laughter frequency such as personality, happiness, life satisfaction, gelotophobia (i.e., fear of being laughed at), and cheerfulness. Validating our new measurement approach (i.e., wearables, physical analogue scale), laughter events elicited higher happiness ratings compared to reference assessments, as expected. On average, participants reported 2.5 belly laughs per day and on every fourth day a fit of laughter. As expected, participants who were happier and more satisfied with their life laughed more frequently than unhappier, unsatisfied participants. Women and younger participants laughed significantly more than men and older participants. Regarding personality, laughter frequency was positively associated with openness and conscientiousness. No significant association was found for gelotophobia, and results for cheerfulness and related concepts were mixed. By using state-of-the-art statistical methods (i.e., recurrent event regression) for the event-based, multi-level data on laughter, we could replicate past results on laughing.
The effects of demand-resource relationship on work-family conflict under Chinese culture: a cross-sectional study
Authors: Li Tianjiao , Helian Zhiwei , Hu Ling , Ma Mengyuan
Published: May 2024

Chinese work and lifestyle are undergoing dramatic changes caused by constantly changing technology and new policies. The demand-resource dynamic relationship, which leads to work-family conflict (WFC), has become increasingly complicated. However, very little is known about the combined effects of different factors from work and family spheres on WFC. This study aims to explore (1) the discrepancy between fit and misfit, (2) the discrepancy of the different degrees of fit, and (3) the discrepancy of the different degrees of misfit from two perspectives: work demand-family resource and work resource-family demand. Data were collected from 745 individuals in China and analyzed using polynomial regression and response surface. The results demonstrate that individuals having low work demand–high family resources experience the lowest WFC, and the fit between work demands and family resources impacts the conflict in a U way. Similarly, high work resource–low family demand results in the lowest WFC; however, the fit between work resources and family demands has negative effects on the conflict. This study took factors from both family and work domains into consideration and explored the effect of their interaction on WFC. By examining the dynamic relationship between demands and resources, adjustments can be made in both domains simultaneously, providing more flexible guidance for management practices that reduce WFC.
Insights into discrepancies in professional identities and role models in undergraduate medical education in the context of affective burden
Authors: Erschens Rebecca , Skrypski Isabelle , Festl-Wietek Teresa , Herrmann-Werner Anne , Adam Sophia Helen , Schröpel Carla , Nikendei Christoph , Zipfel Stephan , Junne Florian
Published: May 2024

Introduction

International evidence strongly suggests that medical students are at high risk of mental health problems. This distress, which can be mediated by a variety of individual, interpersonal and contextual factors within the curriculum, can be mitigated by effective coping strategies and interventions. Central to this discourse is the recognition that the challenges of professional identity formation can contribute significantly to medical students' distress. The focus of our study is therefore to examine discrepancies in professional identities and role models in undergraduate medical education in relation to affective burden.

Methods

Medical students at different stages of university education and high school graduates intending to study medicine were surveyed in a cross-sectional study. The study employed Osgood and Hofstätter's polarity profile to evaluate the self-image of participants, the image of an ideal and real physician, and their correlation with depression (PHQ-9) and anxiety (GAD-7).

Results

Out of the 1535 students recruited, 1169 (76.2%) participated in the study. Students rated their self-image as somewhere between a more critical real image of physicians and a more positive ideal image. Medical students at all training levels consistently rated the ideal image as remaining constant. Significant correlations were found between the professional role models of medical students and affective symptoms, particularly for the discrepancy between the ideal image of a physician and their self-image. Furthermore, 17% and nearly 15% reported significant symptoms of depression and anxiety, respectively.

Discussion

Our study adds to the growing body of knowledge on professional identity formation in medicine and socialisation in the medical environment. The study highlights the importance of discrepancies between self-image and ideal image in the experience of depressive and anxiety symptoms. Primary prevention-oriented approaches should incorporate these findings to promote reflective competence in relation to professional role models and strengthen the resilience of upcoming physicians in medical training.
Open and remotely accessible Neuroplatform for research in wetware computing
Authors: Jordan Fred D. , Kutter Martin , Comby Jean-Marc , Brozzi Flora , Kurtys Ewelina
Published: May 2024

Wetware computing and organoid intelligence is an emerging research field at the intersection of electrophysiology and artificial intelligence. The core concept involves using living neurons to perform computations, similar to how Artificial Neural Networks (ANNs) are used today. However, unlike ANNs, where updating digital tensors (weights) can instantly modify network responses, entirely new methods must be developed for neural networks using biological neurons. Discovering these methods is challenging and requires a system capable of conducting numerous experiments, ideally accessible to researchers worldwide. For this reason, we developed a hardware and software system that allows for electrophysiological experiments on an unmatched scale. The Neuroplatform enables researchers to run experiments on neural organoids with a lifetime of even more than 100 days. To do so, we streamlined the experimental process to quickly produce new organoids, monitor action potentials 24/7, and provide electrical stimulations. We also designed a microfluidic system that allows for fully automated medium flow and change, thus reducing the disruptions by physical interventions in the incubator and ensuring stable environmental conditions. Over the past three years, the Neuroplatform was utilized with over 1,000 brain organoids, enabling the collection of more than 18 terabytes of data. A dedicated Application Programming Interface (API) has been developed to conduct remote research directly via our Python library or using interactive compute such as Jupyter Notebooks. In addition to electrophysiological operations, our API also controls pumps, digital cameras and UV lights for molecule uncaging. This allows for the execution of complex 24/7 experiments, including closed-loop strategies and processing using the latest deep learning or reinforcement learning libraries. Furthermore, the infrastructure supports entirely remote use. Currently in 2024, the system is freely available for research purposes, and numerous research groups have begun using it for their experiments. This article outlines the system’s architecture and provides specific examples of experiments and results.
An enhancement of the Genium™ microprocessor-controlled knee improves safety and different aspects of the perceived prosthetic experience for unilateral and bilateral users
Authors: Klenow Tyler D. , Lundstrom Russell L. , Morris Arri , Patterson Stan , Simpson Chad , Trejo Ernesto G. , Kannenberg Andreas
Published: May 2024

Introduction

Bilateral microprocessor-controlled prosthetic knee (MPK) users have unique needs in traversing environmental barriers compared to unilateral users. An enhancement to the Genium™/Genium X3™ MPK which included an updated ruleset, hydraulics, and new bilateral parameter presets was made to improve safety while stumbling and the smoothness of gait for all users while also improving the experience of bilateral users. The purpose of the study was to evaluate the effectiveness of the enhancements in a sample with unilateral and bilateral amputation.

Methods

A convenience sample of MPK users was recruited from two sites in the USA in two phases. Assessments included the L-Test of Functional Mobility, Activity-specific Balance Confidence Scale, Prosthetic Limb User Survey of Mobility, a study-specific questionnaire, and the Comparative Activities of Daily Living (ADL) Questionnaire. Statistical significance of extracted data was tested with the Wilcoxon Rank-Sum Test for independent data and Wilcoxon Signed-Rank for paired data with an a priori significance level of p < 0.05. Unilateral subjects were age-matched to the group of bilateral subjects for between-groups and within-groups analyses.

Results

Twenty-six subjects (n = 26) were enrolled. Stumble frequency reduced 85% from 16.0 ± 39.7 to 2.4 ± 2.3 (p = 0.008) between baseline and final assessment overall. The bilateral group reported 50% (p = 0.009) and 57% (p = 0.009) greater relative improvement in patient-reported ease and safety, respectively, of completing ADLs compared to the unilateral group. The unilateral group reported residual limb pain and low back pain reduced from 2.3 to 1.4 (p = 0.020) and 3.8 to 1.8 (p = 0.027), respectively, whereas the bilateral group did not.

Discussion

Substantial reductions in stumbles, residual limb pain, and back pain were shown overall. These reductions were driven by the unilateral group who also showed improvements in comfort, exertion, and concentration while walking. The enhancements to the knee likely reduced some gait asymmetry for unilateral users. Improvements in patient-reported ease and safety of completing ADLs were shown overall and were driven by the bilateral group. This study shows further improvement in patient experience is achievable through innovation in MPK technology even for patients who appear to be functioning well.
Reproducibility of freehand vs. foam cast as well as the intrarater reliability of foam cast ultrasound scans assessing the muscle architecture and tissue organization of the gastrocnemius medialis and vastus lateralis muscles
Authors: Lesinski Melanie , Bashford Gregory , Markov Adrian , Risch Lucie , Cassel Michael
Published: May 2024

Background

This study compares the reproducibility of freehand (FH) vs. foam cast (FC) scans and investigates the intrarater reliability of the ultrasound FC muscle architecture and tissue organization measurements of the gastrocnemius medialis (GM) and vastus lateralis (VL) muscles with fixed and repositioning FC scans.

Methods

Thirteen young adults (22 ± 3 years) underwent repeated sagittal B-mode ultrasound measurements of GM and VL. FH, FC, and repositioned FC scans were conducted. Muscle architecture measurements included muscle thickness (MT), pennation angle (PA), and fascicle length (FL). Spatial frequency analysis assessed muscle tissue organization.

Results

MT decreased from 2.1 to 1.8 cm in GM and from 2.4 to 2.2 cm in VL with the FC compared with the FH. Reproducibility between the FH and the FC showed poor to good intraclass correlation coefficients (ICCs) for MT (0.46–0.77) and PA (0.09–0.86) as well as poor to moderate ICCs for FL (0.41), with very low to moderate test–retest variability (TRV) (4%–18%). Tissue organization indicated low to good ICCs (0.21–0.80) with low to moderate TRV (4%–19.5%). The re-scanning results of fixed FC indicated excellent ICCs for MT (0.95–0.996), good for PA (0.77–0.90), and moderate for FL (0.73–0.76), with low TRV (5%–10%) for both muscles. Tissue organization displayed moderate to good ICCs (0.61–0.87) with very low to low TRV (4%–9%). For repositioned FC scans in GM and VL, MT showed good to excellent ICCs (0.86–0.98) with very low to low TRV (2%–8%). PA and FL demonstrated moderate to good ICCs (0.57–0.75), with very low to moderate TRV (2%–13%). Tissue organization revealed ICCs ranging from poor to good (0.13–0.87) for both muscles, with low to moderate TRV (5%–18%).

Conclusion

The FC systematically reduced MT by 2–3 mm. Furthermore, reproducibility revealed low ICCs and high data variability for several muscle architecture and tissue organization parameters. Thus, switching methods within a single study is not recommended. Nevertheless, FC ultrasound scans demonstrated excellent intrarater reliability for assessing MT. In the case of fixed FC scans particularly, moderate to excellent ICCs were observed for all muscle architecture and tissue organization parameters, accompanied by very low to low variability. Therefore, FC scans are recommended for investigating acute effects on muscle architecture and tissue organization when the FC remains on the leg throughout the period of measurements.
A comparative assessment of policy induced diffusion pathways for utility scale solar PV: case study of Indonesia
Authors: Syafina Paramastri , Oluleye Gbemi
Published: May 2024

Lack of effective policies hinder the uptake of Utility-scale solar PV, even though they are projected to play a pivotal role in achieving Indonesia's 2050 net-zero energy target. This study seeks to identify a cost-effective pathway to increase the capacity of utility-scale solar PV in Indonesia through supportive policies that ensure equitable cost distribution between the government and industry. A novel Market Penetration Optimization Model is developed and applied in simulation mode to assess existing policies, and optimization mode to determine new policy recommendations and compare three policy induced diffusion pathways. Results show that current price-based policies are insufficient to stimulate growth in the solar PV market, only covering ~13% of the investment cost required by the industry. Thus, necessitating a reactivation of Feed-in-Tariffs. The optimal tariffs rates required range from 0.39 to 1.47 cents/kWh for the most economic pathway during the initial 10-year post-construction period. The Innovation Diffusion Theory-based pathway necessitates the lowest initial investment cost while yielding the highest revenue from electricity sales, demonstrating its superior cost-effectiveness compared to both the supply-based and linear pathways. This study enriches the literature by exploring the financial implications of policy induced diffusion pathways.
Sensory profiles of Robusta coffee (Coffea canephora) genetic resources from the Democratic Republic of the Congo
Authors: Bollen Robrecht , Verleysen Lauren , Katshela Benjamin Ntumba , Kambale Jean-Léon , Ebele Tshimi , Ruttink Tom , Vandelook Filip , Honnay Olivier , Stoffelen Piet
Published: May 2024

Introduction

The genetic diversity of Robusta coffee (Coffea canephora), a cornerstone in the global coffee industry, remains not fully explored, leading to a significant gap in our understanding of its sensory intricacies. Our study evaluated the sensory quality potential of the Robusta cultivars from the INERA Coffee Collection in Yangambi (the Democratic Republic of the Congo), the local wild diversity, and their hybrids.

Methods

We evaluated the sensory attributes of 70 genotypes representing the genetic structure of the coffee collection. Of those 70, 22 genotypes were evaluated for two consecutive years to assess the consistency of the sensory quality. Standard coffee cupping with the Fine Robusta Standards and Protocols was enhanced through sensory descriptors from the Coffee Taster’s Flavor Wheel. Each genotype’s sensory profile was constructed based on the Total cupping score and the frequency of reported sensory descriptors. The Total cupping score ranged from 75.75 to 84.75, with a substantial variation in sensory profiles, even within a genetic cluster.

Results and discussion

Nutty/Cocoa was the most frequently reported descriptor class. The sensory profile ideotype exhibits a high frequency of Fruity, Sweet, and Sour/Fermented descriptors and a low frequency of Green/Vegetative, Other, and Roasted descriptors. Evidence suggests that the sensory profile of a genotype is consistent over two harvest years. Genotypes with promising and unique sensory profiles were discovered within the cultivars and the wild – cultivar hybrids. The genetic diversity of wild and cultivated Robusta in the Democratic Republic of the Congo could play an essential role in understanding and improving its sensory quality.
Spatio-temporal dynamics and drivers of highly pathogenic avian influenza H5N1 in Chile
Authors: Azat Claudio , Alvarado-Rybak Mario , Aguilera José F. , Benavides Julio A.
Published: May 2024

Introduction

Highly pathogenic avian influenza A H5N1 clade 2.3.4.4b (hereafter H5N1) is causing vast impacts on biodiversity and poultry around the globe. In Chile, lethal H5N1 cases have been reported in a wide range of wild bird species, marine mammals, backyard and industrial poultry, and humans. This study describes the spatio-temporal patterns of the current epizootic of H5N1 in Chile and test drivers that could be associated with outbreak occurrence.

Methods

We used H5N1 cases reported by the Chilean National Animal Health Authority from 5 December 2022 to 5 April 2023. These included wild bird cases confirmed through an avian influenza-specific real-time reverse transcription PCR assay (RT-qPCR), obtained from passive and active surveillance. Data were analyzed to detect the presence of H5N1 clusters under space–time permutation probability modeling, the association of H5N1 with distance and days since the first outbreak through linear regression, and the correlation of H5N1 presence with a number of ecological and anthropogenic variables using general linear modeling.

Results

From 445 H5N1 identified outbreaks involving 613 individual cases in wild birds, a consistent wave-like spread of H5N1 from north to south was identified, which may help predict hotspots of outbreak risk. For instance, seven statistically significant clusters were identified in central and northern Chile, where poultry production and wildlife mortality are concentrated. The presence of outbreaks was correlated with landscape-scale variables, notably temperature range, bird richness, and human footprint.

Discussion

In less than a year, H5N1 has been associated with the unusual mortality of >100,000 individuals of wild animals in Chile, mainly coastal birds and marine mammals. It is urgent that scientists, the poultry sector, local communities, and national health authorities co-design and implement science-based measures from a One Health perspective to avoid further H5N1 spillover from wildlife to domestic animals and humans, including rapid removal and proper disposal of wild dead animals and the closure of public areas (e.g., beaches) reporting high wildlife mortalities.
Oxytocin, prostaglandin F2α, and scopolamine for uterine involution of dairy cows
Authors: Carbonari Alice , Burgio Matteo , Frattina Lorenza , Ceci Edmondo , Sciannamblo Maurizio , Ricci Pasquale , Cicirelli Vincenzo , Rizzo Annalisa
Published: May 2024

The aim of the study was to compare the effect of three substances with ecbolic activity, Oxytocin, Prostaglandin F2α (PGF2α) and Scopolamine, on the uterine involution process in dairy cows and on the resumption of ovarian activity. Eighty bovine were randomly divided in four groups: GROUP C: 20 cows treated, within 24 h of calving, with 5 mL/head of saline solution; GROUP PG: 20 cows treated, within 24 h of calving, with 150 μg/head of d-cloprostenol; GROUP OX: 20 cows treated, within 24 h of calving, with 50 IU/head of oxytocin acetate; GROUP S: 20 cows treated, within 24 h of calving, with 40 mg/q Scopolamine Butylbromide. Each cow was subjected to blood samples to evaluate the Hydroxyproline (HYP) levels, at T0, within 24 h after calving, and T7, T14, T28, 7, 14, and 28 days after calving, respectively. At T14 and T28, an ultrasound examination was performed to measure the diameter of ex-pregnant horn. In all cows, the reproductive indices (days to first service and number of artificial insemination for conception) were evaluated. In all groups, the HYP concentrations have been rising from T0 to T28, with the maximum levels obtained at T28 in the groups PG and S. As regard the diameter of uterine horn, the comparison among the groups showed significant differences only at T28, with lower values in the group PG and S. In group S and PG, the days to first service were less than other groups. Treatment with Scopolamine and PGF2α resulted in better outcomes, evidenced clinically by more efficient uterine involution and faster ovarian recovery.
Design and Implementation of an L1 Adaptive Proportional Output Feedback Controller
Authors: Bagati Deepanshu , Souanef Toufik , Whidborne James F.
Published: May 2024

A new approach for output feedback L1 adaptive control based on a proportional adaptation law is presented. The effectiveness of this design is assessed in simulation and validated through real-time testing on an airfoil pitch control wind tunnel experimental rig. Experimental evaluation of the robustness of the controllers, assessed by introducing various disturbances into the control signals, shows that the adaptive control has a better performance compared to PID control, particularly in scenarios with reduced control effectiveness and time-varying disturbances. The experimental results demonstrate the efficacy of the proposed method in practical applications.