bluuebunny/crossref_metadata_2025 huggingface dataset:
Common bile duct perforation due to choledocholithiasis in a cat with gallbladder agenesis
Authors: Noguchi Aki , Iwanaga Tomoko , Miura Naoki , Sogawa Takeshi , Fujiki Makoto
Published: February 2023

Case summary

An 8-year-old neutered male domestic shorthair cat was presented for further investigation of anorexia, vomiting and lethargy. Abdominal ultrasonography and contrast-enhanced CT revealed choledocholithiasis with suspected bacterial peritonitis and non-visualisation of the gallbladder. During surgery, the common bile duct was noted to be perforated, and a cholelith was found in the abdominal cavity. No gallbladder was confirmed during surgery. Three months postoperatively, the cat underwent CT cholangiography and absence of the gallbladder with a vestigial duplicated gallbladder was diagnosed.

Relevance and novel information

Gallbladder agenesis is extremely rare in cats, with only one previous report, but several dogs have been diagnosed based on CT cholangiography and laparoscopy. This report describes gallbladder agenesis concurrent with choledocholithiasis in an adult cat and represents the first report of CT cholangiography in a cat with gallbladder agenesis.
Understanding Consumer Environmental Ethics and the Willingness to Use Green Products
Authors: Alam Mohammad Nurul , Ogiemwonyi Osarodion , Hago Ibrahim. E. , Azizan Noor Azlinna , Hashim Fariza , Hossain Md Sazzad
Published: February 2023

Environmental ethics and moral obligation are action plan that helps to preserve the environment and has influenced consumption style. The utilization of green products and consumption has helped minimize environmental and health threats, which is considered to sustain the environment. In this study, we examine consumer environmental ethics, environmental attitude, social influence, and moral obligation through the mediation of the willingness to use green products toward green behavior. Using a questionnaire survey method to capture 250 consumers in Abuja, Nigeria and SmartPLS3.0 to assess the model validity. The outcomes of our study show that consumer environmental ethics, environmental attitude, and moral obligation positively influence willingness to use green products, which also influence green behavior. The mediating effect was established and willingness to use green products simultaneously mediates the relationships between consumer environmental ethics, environmental attitude, moral obligation and green behavior. Further, social influence does not predict willingness to use green products, and the mediating link between social influence and green behavior was not supported. The study provides implications based on the empirical findings for theoretical and managerial insight as well as for future research.
Trolligans: Conceptual Links Between Trolling and Hooliganism in Sports and Esports
Authors: Cook Christine L. , Karhulahti Veli-Matti , Harrison Guy , Bowman Nicholas D.
Published: February 2023

Both game-based trolling and hooliganism have existed in some form since the inception of online gaming and professional sports respectively. The two share many characteristics: provocation of an opposing entity, the tendency to taunt or trash-talk others based on their social or individual identity, and disruptive and/or destructive behaviour. However, despite this and the increasing similarity between the worlds of traditional sports and esports, research on the two negatively perceived phenomena has remained largely separate. The present article aims to both link and distinguish the two types of behaviour in terms of what motivates them, the agents involved, and the spaces in which they take place. By drawing from communication theories and cases described as both hooliganism and trolling in professional sports and esports settings, we (a) refine the definition of trolling in light of hooliganism, (b) discuss practical implications for the future health of esports communities, and (c) explore deviance as inherent entertainment in mediatised sporting events. Suggestions for future collaborative research between trolling and hooliganism specialists are also included.
Comparison of single taper and dual taper versions of the same stem design in total hip arthroplasty for primary osteoarthritis
Authors: Castagnini Francesco , Bordini Barbara , Cosentino Monica , Tassinari Enrico , Guizzardi Giulia , Traina Francesco
Published: February 2023

Background

In total hip arthroplasty (THA), the outcomes of single taper (ST) and dual taper (DT) versions of the same stem design have been scarcely studied. A registry study comparing ST and DT versions of the same stem design was designed, aiming to assess: (1) the survival rates and the hazard ratios for failure; (2) the survival rates and the hazard ratios for failure using stem-focused endpoints.

Material and methods

A regional arthroplasty registry was interrogated about stem designs with ST and DT versions in cementless THAs performed for primary osteoarthritis. Only the same cup and ceramic-on-ceramic bearings were included: the DT stems had a titanium-on-titanium modularity. Demographic and implant features were recorded. Survival rates and hazard ratios were evaluated and compared. Stem-focused endpoints were also investigated.

Results

A total of 5359 THAs were included, with three stem designs. The two versions of every stem showed different demographics and implant-related features: ST versions were preferentially implanted in heavier young men. For each stem, the two versions had similar survival rates at 5 years (p = 0.076; p = 0.319; p = 0.616) and similar adjusted hazard ratios for failures (p = 0.084; p = 0.308; p = 0.729). When stem-focused endpoints were adopted, the ST and DT versions of the three stems achieved similar survival rates (p = 0.710; p = 0.784; p = 0.983) and similar adjusted hazard ratios (p = 0.647; p = 0.858; p = 0.787). Three neck breakages occurred (0.0007% of all the modular implants).

Conclusions

ST and DT versions of the same stem design did not show any differences in terms of survival rates and hazard ratios for failures at 5 years.

LEVEL OF EVIDENCE: IV.
Phylogeny and adaptive evolution of subgenus Rhizirideum (Amaryllidaceae, Allium) based on plastid genomes
Authors: Fu Xiao , Xie Deng-Feng , Zhou Yu-Yang , Cheng Rui-Yu , Zhang Xiang-Yi , Zhou Song-dong , He Xing-Jin
Published: February 2023

The subgenus Rhizirideum in the genus Allium consists of 38 species worldwide and forms five sections (A. sect. Rhizomatosa, A. sect. Tenuissima, A. sect. Rhizirideum, A. sect. Eduardia, and A. sect. Caespitosoprason), A. sect. Caespitosoprason being merged into A. sect. Rhizomatosa recently. Previous studies on this subgenus mainly focused on separate sections. To investigate the inter-section and inter-subgenera phylogenetic relationships and adaptive evolution of A. subg. Rhizirideum, we selected thirteen representative species, which cover five sections of this subgenus and can represent four typical phenotypes of it. We conducted the comparative plastome analysis with our thirteen plastomes. And phylogenetic inferences with CDSs and complete sequences of plastomes of our thirteen species and another fifty-four related species were also performed. As a result, the A. subg. Rhizirideum plastomes were relatively conservative in structure, IR/SC borders, codon usage, and repeat sequence. In phylogenetic results, the inter-subgenera relationships among A. subg. Rhizirideum and other genus Allium subgenera were generally similar to the previous reports. In contrast, the inter-section relationships within our subgenus A. subg. Rhizirideum were newly resolved in this study. A. sect. Rhizomatosa and A. sect. Tenuissima were sister branches, which were then clustered with A. sect. Rhizirideum and A. sect. Eduardia successively. However, Allium Polyrhizum Turcz. ex Regel, type species of A. sect. Caespitosoprason, was resolved as the basal taxon of A. subg. Rhizirideum. Allium siphonanthum J. M. Xu was also found in clade A. subg. Cyathophora instead of clade A. subg. Rhizirideum. The selective pressure analysis was also conducted, and most protein-coding genes were under purifying selection. At the same time, just one gene, ycf2, was found under positive selection, and another three genes (rbcL, ycf1a, ycf1b) presented relaxed selection, which were all involved in the photosynthesis. The low temperature, dry climate, and high altitude of the extreme habitats where A. subg. Rhizirideum species grow might impose intense natural selection forces on their plastome genes for photosynthesis. In summary, our research provides new insights into the phylogeny and adaptive evolution of A. subg. Rhizirideum. Moreover, we suggest that the positions of the A. subg. Rhizirideum species A. polyrhizum and A. siphonanthum should be reconsidered.
The effect of all-cause hospitalization on cognitive decline in older adults: a longitudinal study using databases of the National Health Insurance Service and the memory clinics of a self-run hospital
Authors: Park Dougho , Kim Hyoung Seop , Kim Jong Hun
Published: February 2023

Background

Cognitive decline is common in older adults and imposes a burden on public health. Especially for older adults, hospitalization can be related to decreased physical fitness. This study aimed to investigate the quantitative association between hospitalization and cognitive decline.

Methods

This was a retrospective cohort study. We performed a longitudinal study by using the combined database from the Korean National Health Insurance Service (NHIS) and memory clinic data of its self-run hospital. We identified whether hospitalized, the number of hospitalizations, and the total hospitalization days through the claim information from the NHIS database. We also identified whether hospitalization was accompanied by delirium or surgery with general anesthesia for subgroup analysis. Primary outcome was the clinical dementia rating-sum of boxes (CDR-SB) score. Secondary outcomes were mini-mental state examination (MMSE) score, clinical dementia rating (CDR) grade, and Korean-instrumental activities of daily living (KIADL) score. Multivariable mixed models were established.

Results

Of the 1810 participants, 1200 experienced hospitalization at least once during the observation period. The increase in CDR-SB was significantly greater in the hospitalized group (β = 1.5083, P < .001). The same results were seen in the total number of hospitalizations (β = 0.0208, P < .001) or the total hospitalization days (β = 0.0022, P < .001) increased. In the group that experienced hospitalization, cognitive decline was also significant in terms of CDR grade (β = 0.1773, P < .001), MMSE score (β = − 1.2327, P < .001), and KIADL score (β = 0.2983, P < .001). Although delirium (β = 0.2983, P < .001) and nonsurgical hospitalization (β = 0.2983, P < .001) were associated with faster cognitive decline, hospitalization without delirium and with surgery were also related to faster cognitive decline than in the no hospitalization group.

Conclusion

Cognitive decline was quantitatively related to all-cause hospitalization in older adults. Moreover, hospitalizations without delirium and surgery were also related to cognitive decline. It is vital to prevent various conditions that need hospitalization to avoid and manage cognitive dysfunction.
Clinical efficacy and re-pregnancy outcomes of patients with previous cesarean scar pregnancy treated with either high-intensity focused ultrasound or uterine artery embolization before ultrasound-guided dilatation and curettage: a retrospective cohort study
Authors: Wang Xi , Yang Bing , Chen Wenzhi , Chen JinYun
Published: February 2023

Background

Cesarean scar pregnancy (CSP) treated with either high-intensity focused ultrasound ablation (HIFU-a) or uterine artery embolization (UAE) combined with ultrasound-guided dilation and curettage (USg-D&C) was effective. However, there is insufficient comparative research evidence on clinical efficacy and subsequent pregnancy outcomes after previous CSP treatment. This study aims to investigate the efficacy, safety, and subsequent pregnancy outcomes of HIFU-a compared to UAE before USg-D&C for the treatment of CSP.

Methods

Between January 2016 and July 2020, a total of 272 patients received the pretreatment with HIFU-a or UAE(HIFU-a group: n = 118; UAE group: n = 154). The clinical characteristics, treatment success rate, postoperative pregnancy rate and outcome of the two groups were compared and analyzed.

Results

The demographic characteristics of the two groups were similar. After pretreatment, the adverse events rate of HIFU-a group was lower than that of UAE group (10.40% (16/154) vs. 40.70% (48/118), P = 0.00). All patients received the USg-D&C. The HIFU-a group was of less intraoperative blood loss (10.00 (5.00–20.00) vs. 12.50 (5.00–30.00) ml, P = 0.03). There was no statistically significant difference between the two groups in success rates. However, the HIFU-a group was of a shorter duration of postoperative vaginal bleeding (12.00 (9.00–13.00) vs. 14.00 (12.00–15.00) days, P = 0.00). There was no significant difference between the two groups in terms of subsequent pregnancy rates (P = 0.317). However, the recurrent CSP (rCSP) rate in the HIFU-a group was lower than that in the UAE group (7.70% (6/78) vs. 19.70%(13/66), P = 0.03).

Conclusions

CSP treated with either HIFU-a or UAE combined with USg-D&C was safe and effective. Although no significant difference was found in the subsequent pregnancy outcomes of the two groups, the rCSP was more common in the UAE group. So, we recommend HIFU-a combined with USg-D&C treatment modality.
Routine binocular examination of young Taiwanese adults as a predictor of visual behavior performance
Authors: Chen Shyan-Tarng , Su Kuo-Chen , Wang Po-Hsin , Zhong Xiang-Yin , Cheng Ching-Ying
Published: February 2023

Background

Morgan and Scheiman’s Optometric Extension Program (OEP) expected binocular vision findings have longstanding use in optometry. With technological advances, the demands and standards of binocular function have changed. This study aimed to investigate which binocular visual functions can effectively predict visual behavior performance.

Methods

Participants aged 15–24 years were recruited from two colleges and two universities. After completing the CSMU-Visual Behavioral Performance questionnaire (CSMU-VBP, with four components: near work, visual perception, visual comfort, and whole-body balance), participants were divided into symptomatic and asymptomatic groups based on questionnaire findings (cutoff: < 12 vs. ≥ 12 symptoms). Then a 24-step binocular visual examination was undertaken. Data were analyzed with one-sample, Student’s, and paired t-tests. Additionally, receiver operating characteristic analysis was used to determine the predictors of binocular visual function required for near work, visual perception, visual comfort, and body balance dimensions.

Results

Among 308 participants, 43 (14%) and 265 (86%) were symptomatic and asymptomatic, respectively. Among the 46 participants with abnormal binocular vision, 36 (78%) reported that they had no obvious symptoms. The commonest dysfunctions were accommodative excess and convergence excess. Most of the binocular visual findings significantly diverged from traditional normal values: amplitude of accommodation, as well as base-in prism to break and recovery points at distance were higher than traditional normal values, whereas others were lower than traditional normal values. Total CSMU-VBP scores indicated that the asymptomatic and symptomatic groups had significant differences in DBO recovery (t = 2.334, p = 0.020) and BAF (t = 1.984, p = 0.048). Receiver operating characteristic curve analysis yielded the following binocular visual functional cutoff points: near work (DBO blur < 7, DBO recovery < 5.5), visual perception (MAF < 10.5, BAF < 10.25), visual comfort (DLP <  − 2.25, DBI break > 11.5, NBI blur > 15, NBI break > 17.5, NBI recovery > 13, NPC < 5.75), and body balance (NFD_H >  − 0.5, gradient AC/A [minus] > 2.25, NPC < 4.75).

Conclusions

The mean values of binocular visual function among young Taiwanese adults were statistically different from traditional normative values. Further research is required to confirm whether these findings reflect impaired binocular vision or stringent criteria. Assessments of binocular visual function, especially binocular accommodation sensitivity, are crucial in routine optometric examination.
Proliferative diabetic retinopathy and diabetic macular edema are two factors that increase macrophage-like cell density characterized by en face optical coherence tomography
Authors: Wang Wenyu , Sun Gongpeng , Xu Amin , Chen Changzheng
Published: February 2023

Background

Macrophage-like cells (MLCs) located at the ILM were observed in live human retinas using adaptive optics optical coherence tomography (OCT) as well as clinically-used OCT. The study aimed to quantitatively analyzing MLCs at the vitreoretinal interface (VRI) in diabetic retinopathy (DR) using en face OCT and swept-source optical coherence tomography angiography (SS-OCTA).

Methods

190 DR eyes were included in the study, with 70 proliferative diabetic retinopathy (PDR) eyes and 120 non- proliferative diabetic retinopathy (NPDR) eyes. Sixty-three eyes from normal subjects were included as controls. MLCs were visualized in a 5 μm en face OCT slab above the VRI centered on the fovea. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the OCTA parameters and the MLC parameters among groups. We evaluated the MLC density among groups on binarized images after image processing. We also investigated the relationship between MLC density and other OCT parameters including retina thickness and vessel density (VD).

Results

The MLC density significantly increased in PDR eyes (PDR vs. NPDR, 8.97 (8.40) cells/mm2 vs.6.14 (8.78) cells/mm2, P = 0.013; PDR vs. normal, 8.97 (8.40) cells/mm2vs. 6.48 (6.71) cells/mm2, P = 0.027) and diabetic macular edema (DME) eyes (DME vs. without DME, 8.94 (8.26) vs.6.09 (9.00), P = 0.005). After adjusting for age and gender, MLC density in NPDR eyes negatively correlated to VD of deep capillary plexus (DCP) (P = 0.01).

Conclusions

SS-OCTA is a non-invasive and simple method for the characterization of MLCs at the VRI. PDR and DME are two factors that increase MLC density. MLC density also correlated with VD.
“Ancestral recipes”: a mixed-methods analysis of MyPlate-based recipe dissemination for Latinos in rural communities
Authors: Cheney Ann Marie , McCarthy William J. , Pozar María , Reaves Christina , Ortiz Gabriela , Lopez Diana , Saldivar Perla A. , Gelberg Lillian
Published: February 2023

Background

The Latinx population experiences some of the highest rates of chronic disease, including obesity and type II diabetes. Such conditions may be especially burdensome in rural Latinx communities that often face barriers to accessing disease prevention resources and public health programs.

Methods

Diverse stakeholders (i.e., patients, community members, system of healthcare clinics, community food bank) tailored an existing cookbook, based on the U.S. Department of Agriculture MyPlate healthy eating and dietary guidelines, for local ingredients, health literacy, and language for rural Latinx and Indigenous Latin Americans. The cookbook recipes were disseminated widely via virtual cooking demonstrations, food distribution events, and social media. Pre- and posttest surveys were used to assess changes in diabetes knowledge measured by the 24-item American Diabetes Association Diabetic Knowledge Questionnaire and confidence in dietary behavior change over time measured by 4 questions of the 17-item Mediterranean Diet Index. A mixed effects, repeated measures analysis was conducted with gender ID, age range and educational attainment included as covariates and assessment interval as the predictor (pretest vs posttest) and change in confidence about adhering to four specific components of the Mediterranean diet. Focus groups elicited information on participants’ motivation and ability to use the recipes and eat healthy foods following the virtual cooking demonstration participation.

Results

A total of 20 virtual cooking demonstrations were conducted and 60 participants completed a pretest survey and 54 a posttest survey, a subsample (n = 19) participated in one of three focus groups. Most participants were female, identified as Latinx/Hispanic, were between the ages of 40-49, and spoke Spanish. 17% identified as Indigenous Latin American specifically as Purépecha, an indigenous group from Michoacán, Mexico. Survey and focus group findings indicated at posttest an increase in diabetes knowledge among participants with no prior diagnosis of chronic health conditions and more confidence in limiting sugary beverages and refined wheat pasta/white rice among indigenous participants. Focus group discussions explicated the quantitative findings.

Conclusion

This study brought together patients and key stakeholders committed to addressing the social determinants of health and it mobilized the community to develop culturally vetted health education materials. The findings indicate the need for increased access to evidence-based nutrition education and to culturally appropriate food products that can be easily incorporated into daily food preparation.
COVID-19 and the elaboration of personal plans in + 50: a Brazilian experience
Authors: Garcia Kerolyn Ramos , Bento Andrea Pecce , de Oliveira Aline Gomes , da Silva Rafaela Alves , Chiarello Marileusa Dosolina , Chariglione Isabelle Patriciá Freitas Soares , Karnikowski Margô Gomes de Oliveira
Published: February 2023

Background

In front of the physical and social isolation, as well as feelings of fear and instability imposed by the pandemic of COVID-19, especially for risk groups such as people 50 + , it became even more relevant to discuss the formulation of personal plans for this age population. This study aimed to analyse the individual plans of people 50 + , considering their perception, feelings and life experiences during the COVID-19 pandemic.

Methods

This is a mixed study (quali-quantitative), using Minayo’s methodology for content analysis and frequency analyses, made with 39 participants from the University of Brasília Educational Program, Universidade do Envelhecer – UniSER/UnB. We used a word cloud system and a wheel of life tool to showcase the results.

Results

Analysing professional achievements and situations participants want to overcome, the categories of feelings that stand out were Loving Relationships, Sadness, Family Absence, Grief, Trauma and Regret. Intellectual Development, Personal Fulfilment, Purpose and Creativity, Hobbies and Fun were the most mentioned personal plans displayed by the wheel of life. The key personal changes mentioned were to be less shy, prioritise themselves, change how they interact with others, and focus on their health.

Conclusions

This study concludes that perception, feelings and life experiences during the COVID-19 pandemic did not seem to directly affect the path in elaborating personal plans.
Assessment of paper dust exposure and chronic respiratory symptoms among paper factory workers in, Ethiopia; a comparative cross-sectional study
Authors: Negash Bereket Meskele , Abaya Samson Wakuma , Abegaz Teferi , Takele Abera Kumie , Mekonnen Worku Tefera , Negatu Hager Badima , Gintamo Tamene Tesema , Tamirat Teshome , Koirita Gelaneh Kusse
Published: February 2023

Background

Workers in pulp and paper factories are continuously exposed to paper dust. Excessive exposure to paper dust can cause respiratory disease. Information about the prevalence of chronic respiratory symptoms and dust exposure levels among workers in pulp and paper factories is not available in Ethiopia. The aim of this study was, therefore, to assess personal total dust exposure levels, the prevalence of chronic respiratory symptoms and their associated risk factors among workers in Ethiopian pulp and paper factories.

Methods

A comparative cross-sectional study was conducted. A total of 40 dust measurements were carried out on 20 randomly selected workers. To assess chronic respiratory symptoms and associated factors, 434 workers from two paper factories and controls were interviewed using a standard questionnaire adapted from the American Thoracic Society (ATS). Gravimetric analyses of the filters were undertaken using a standard microbalance. Poisson regression was performed for comparing the prevalence of symptoms and risk factors for the two groups. Multivariable analyses were conducted to identify factors associated with chronic respiratory symptoms.

Result

The arithmetic mean (AM) and geometric mean (GM) of dust exposure levels among the paper factories workers were 11.3 (± 7.7) and 10.2 (± 1.4) mg/m3 respectively. This exposure level exceeded the threshold limit value recommended for total dust (10 mg/m3). The prevalence of having at least one chronic respiratory symptom was about 51% among the workers in paper factories. The prevalence ratio of having chronic respiratory symptoms among paper factory workers was 5.6 times higher (PR = 6, 95% CI 3.5–10.3) than in the controls. Chronic respiratory symptoms were significantly associated with factors such as an educational status of less than grade 9, being employed in the work sections of the factories, having work experience of 5 years and above, working more than 8 h per day and having a past history of occupation and respiratory illnesses.

Conclusion

The dust concentration in the paper factories exceeded the acceptable recommended limit value of 10 mg/m3. The prevalence of chronic respiratory symptoms among paper factory workers was higher than among controls. The main determining factors for chronic respiratory symptoms among the workers were the specific work section such as production section, low income, having past history of respiratory illnesses, the number of years of working and low educational status. This finding indicated the need for improving the working conditions in paper factories in Ethiopia.
A first step towards a framework for interventions for individual working practice to prevent work-related musculoskeletal disorders: a scoping review
Authors: van de Wijdeven Bert , Visser Bart , Daams Joost , Kuijer Paul P.F.M.
Published: February 2023

Background

Work-related musculoskeletal disorders (WMSDs) are a key topic in occupational health. In the primary prevention of these disorders, interventions to minimize exposure to work-related physical risk factors are widely advocated. Besides interventions aimed at the work organisation and the workplace, interventions are also aimed at the behaviour of workers, the so-called individual working practice (IWP). At the moment, no conceptual framework for interventions for IWP exists. This study is a first step towards such a framework.

Methods

A scoping review was carried out starting with a systematic search in Ovid Medline, Ovid Embase, Ovid APA PsycInfo, and Web of Science. Intervention studies aimed at reducing exposure to physical ergonomic risk factors involving the worker were included. The content of these interventions for IWP was extracted and coded in order to arrive at distinguishing and overarching categories of these interventions for IWP.

Results

More than 12.000 papers were found and 110 intervention studies were included, describing 810 topics for IWP. Eventually eight overarching categories of interventions for IWP were distinguished: (1) Workplace adjustment, (2) Variation, (3) Exercising, (4) Use of aids, (5) Professional skills, (6) Professional manners, (7) Task content & task organisation and (8) Motoric skills.

Conclusion

Eight categories of interventions for IWP are described in the literature. These categories are a starting point for developing and evaluating effective interventions performed by workers to prevent WMSDs. In order to reach consensus on these categories, an international expert consultation is a necessary next step.
Formation and characterization of BMP2/GDF5 and BMP4/GDF5 heterodimers
Authors: Gipson Gregory R. , Nolan Kristof , Kattamuri Chandramohan , Kenny Alan P. , Agricola Zachary , Edwards Nicole A. , Zinski Joseph , Czepnik Magdalena , Mullins Mary C. , Zorn Aaron M. , Thompson Thomas B.
Published: February 2023

Background

Proteins of the TGFβ family, which are largely studied as homodimers, are also known to form heterodimers with biological activity distinct from their component homodimers. For instance, heterodimers of bone morphogenetic proteins, including BMP2/BMP7, BMP2/BMP6, and BMP9/BMP10, among others, have illustrated the importance of these heterodimeric proteins within the context of TGFβ signaling.

Results

In this study, we have determined that mature GDF5 can be combined with mature BMP2 or BMP4 to form BMP2/GDF5 and BMP4/GDF5 heterodimer. Intriguingly, this combination of a BMP2 or BMP4 monomer, which exhibit high affinity to heparan sulfate characteristic to the BMP class, with a GDF5 monomer with low heparan sulfate affinity produces a heterodimer with an intermediate affinity. Using heparin affinity chromatography to purify the heterodimeric proteins, we then determined that both the BMP2/GDF5 and BMP4/GDF5 heterodimers consistently signaled potently across an array of cellular and in vivo systems, while the activities of their homodimeric counterparts were more context dependent. These differences were likely driven by an increase in the combined affinities for the type 1 receptors, Alk3 and Alk6. Furthermore, the X-ray crystal structure of BMP2/GDF5 heterodimer was determined, highlighting the formation of two asymmetric type 1 receptor binding sites that are both unique relative to the homodimers.

Conclusions

Ultimately, this method of heterodimer production yielded a signaling molecule with unique properties relative to the homodimeric ligands, including high affinity to multiple type 1 and moderate heparan binding affinity.
Folylpolyglutamate synthetase mRNA G-quadruplexes regulate its cell protrusion localization and enhance a cancer cell invasive phenotype upon folate repletion
Authors: Stark Michal , Levin May , Ulitsky Igor , Assaraf Yehuda G.
Published: February 2023

Background

Folates are crucial for the biosynthesis of nucleotides and amino acids, essential for cell proliferation and development. Folate deficiency induces DNA damage, developmental defects, and tumorigenicity. The obligatory enzyme folylpolyglutamate synthetase (FPGS) mediates intracellular folate retention via cytosolic and mitochondrial folate polyglutamylation. Our previous paper demonstrated the association of the cytosolic FPGS (cFPGS) with the cytoskeleton and various cell protrusion proteins. Based on these recent findings, the aim of the current study was to investigate the potential role of cFPGS at cell protrusions.

Results

Here we uncovered a central role for two G-quadruplex (GQ) motifs in the 3′UTR of FPGS mediating the localization of cFPGS mRNA and protein at cell protrusions. Using the MBSV6-loop reporter system and fluorescence microscopy, we demonstrate that following folate deprivation, cFPGS mRNA is retained in the endoplasmic reticulum, whereas upon 15 min of folate repletion, this mRNA is rapidly translocated to cell protrusions in a 3′UTR- and actin-dependent manner. The actin dependency of this folate-induced mRNA translocation is shown by treatment with Latrunculin B and inhibitors of the Ras homolog family member A (RhoA) pathway. Upon folate repletion, the FPGS 3′UTR GQs induce an amoeboid/mesenchymal hybrid cell phenotype during migration and invasion through a collagen gel matrix. Targeted disruption of the 3′UTR GQ motifs by introducing point mutations or masking them by antisense oligonucleotides abrogated cell protrusion targeting of cFPGS mRNA.

Conclusions

Collectively, the GQ motifs within the 3′UTR of FPGS regulate its transcript and protein localization at cell protrusions in response to a folate cue, inducing cancer cell invasive phenotype. These novel findings suggest that the 3′UTR GQ motifs of FPGS constitute an attractive druggable target aimed at inhibition of cancer invasion and metastasis.
The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study
Authors: Taylor Kurt , Wootton Robyn E. , Yang Qian , Oddie Sam , Wright John , Yang Tiffany C. , Magnus Maria , Andreassen Ole A. , Borges Maria Carolina , Caputo Massimo , Lawlor Deborah A.
Published: February 2023

Background

Congenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference.

Methods

Three birth cohorts, including 65,510 mother/offspring pairs (N = 562 CHD cases) were included. We used Mendelian randomisation (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large-scale genome-wide association studies (GWAS) and validated the strength and relevance of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) higher GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings.

Results

The GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 0.95 (0.88, 1.03)), lifetime smoking (pooled OR: 1.01 (0.93, 1.09)) and alcoholic drinks per week (pooled OR: 1.06 (0.98, 1.15)) were close to the null. Sensitivity analyses yielded similar results.

Conclusions

Our results do not provide robust evidence of an effect of maternal BMI, smoking or alcohol on offspring CHDs. However, results were imprecise. Our findings need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.
Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality
Authors: O’Loughlin Jessica , Casanova Francesco , Fairhurst-Hunter Zammy , Hughes Amanda , Bowden Jack , Watkins Edward R. , Freathy Rachel M. , Millwood Iona Y. , Lin Kuang , Chen Zhengming , Li Liming , Lv Jun ,   China Kadoorie Biobank Collaborative Group, Walters Robin G. , Howe Laura D. , Kuchenbaecker Karoline , Tyrrell Jessica
Published: February 2023

Background

Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depression in people of East Asian ancestry.

Methods

Multiple Mendelian randomisation (MR) methods were used to test the relationship between (a) BMI and (b) waist-hip ratio (WHR) with depression. Firstly, we performed two-sample MR using genetic summary statistics from a recent genome-wide association study (GWAS) of depression (with 15,771 cases and 178,777 controls) in people of East Asian ancestry. We selected 838 single nucleotide polymorphisms (SNPs) correlated with BMI and 263 SNPs correlated with WHR as genetic instrumental variables to estimate the causal effect of BMI and WHR on depression using the inverse-variance weighted (IVW) method. We repeated these analyses stratifying by home location status: China versus UK or USA. Secondly, we performed one-sample MR in the China Kadoorie Biobank (CKB) in 100,377 participants. This allowed us to test the relationship separately in (a) males and females and (b) urban and rural dwellers. We also examined (c) the linearity of the BMI-depression relationship.

Results

Both MR analyses provided evidence that higher BMI was associated with lower odds of depression. For example, a genetically-instrumented 1-SD higher BMI in the CKB was associated with lower odds of depressive symptoms [OR: 0.77, 95% CI: 0.63, 0.95]. There was evidence of differences according to place of residence. Using the IVW method, higher BMI was associated with lower odds of depression in people of East Asian ancestry living in China but there was no evidence for an association in people of East Asian ancestry living in the USA or UK. Furthermore, higher genetic BMI was associated with differential effects in urban and rural dwellers within China.

Conclusions

This study provides the first MR evidence for an inverse relationship between BMI and depression in people of East Asian ancestry. This contrasts with previous findings in European populations and therefore the public health response to obesity and depression is likely to need to differ based on sociocultural factors for example, ancestry and place of residence. This highlights the importance of setting-specific causality when using genetic causal inference approaches and data from diverse populations to test hypotheses. This is especially important when the relationship tested is not purely biological and may involve sociocultural factors.
In silico formulation of a next-generation multiepitope vaccine for use as a prophylactic candidate against Crimean-Congo hemorrhagic fever
Authors: Alam Rahat , Samad Abdus , Ahammad Foysal , Nur Suza Mohammad , Alsaiari Ahad Amer , Imon Raihan Rahman , Talukder Md. Enamul Kabir , Nain Zulkar , Rahman Md. Mashiar , Mohammad Farhan , Karpiński Tomasz M.
Published: February 2023

Background

Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease transmitted to humans and livestock animals through the bite of infected ticks or close contact with infected persons’ blood, organs, or other bodily fluids. The virus is responsible for severe viral hemorrhagic fever outbreaks, with a case fatality rate of up to 40%. Despite having the highest fatality rate of the virus, a suitable treatment option or vaccination has not been developed yet. Therefore, this study aimed to formulate a multiepitope vaccine against CCHF through computational vaccine design approaches.

Methods

The glycoprotein, nucleoprotein, and RNA-dependent RNA polymerase of CCHF were utilized to determine ﻿immunodominant﻿ T- and B-cell epitopes. Subsequently, an integrative computational vaccinology approach was used to formulate a multi-epitopes vaccine candidate against the virus.

Results

After rigorous assessment, a multiepitope vaccine was constructed, which was antigenic, immunogenic, and non-allergenic with desired physicochemical properties. Molecular dynamics (MD) simulations of the vaccine-receptor complex show strong stability of the vaccine candidates to the targeted immune receptor. Additionally, the immune simulation of the vaccine candidates found that the vaccine could trigger real-life-like immune responses upon administration to humans.

Conclusions

Finally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF.
The challenges of pig farming in Hong Kong: a study of farmers’ perceptions and attitudes towards a pig health and production management service
Authors: Rosanowski Sarah M. , Magouras Ioannis , Ho Wing-Chung , Yiu Wing Chi Jacqueline , Pfeiffer Dirk U. , Zeeh Friederike
Published: February 2023

Background

Pig farming in Hong Kong differs markedly from other places in the world, with a highly urbanised population, the majority of pigs being imported for slaughter, and limited on-farm veterinary support. Little is known about the barriers and attitudes of pig farmers in Hong Kong and their expectations of a new pig health and production management service provided by veterinarians. We collected qualitative and quantitative data to 1) describe pig farms, 2) identify barriers to pig farming in Hong Kong and 3) describe the perceptions of the new service. Thematic analysis was conducted to identify barriers and attitudes.

Results

Eight and nine out of 38 pig farmers agreed to participate in the qualitative and quantitative components, respectively. All farms were farrow-to-finish farms with a median of 2800 (range 950 to 7000) pigs per farm. Three themes were identified during the interview analysis and could be ranked based on their importance to the farmers: the regulatory environment (Theme 1), veterinary support structures (Theme 2), and the sustainability of the pig industry (Theme 3). Farmers expressed dissatisfaction with the regulation of the industry and veterinary services on offer within Hong Kong. However, farmers did note that the provision of a new pig health and production management service was as a positive development. The public perception of pig farming, market forces, and competition from mainland pig farmers have resulted in sustainability challenges for the industry.

Conclusions

Farmers identified very specific local systems and challenges unique to pig farming in Hong Kong. The lack of veterinary support was one of these challenges and although a certain level of scepticism towards the new pig health and production service was expressed, farmers indicated their interest and listed areas where they would benefit from improved veterinary support. Prior experiences of veterinary services clouded farmers perceptions of the usefulness of a new service. To be successful in this environment, clear communication about the goals, role and limitations of the new on farm service is crucial, as is the alignment with the needs of farmers. Despite the small sample size, the qualitative methodology used allows us to assume that these themes give a general idea of what Hong Kong farmers’ concerns and attitudes are.
X chromosome associations with chronic obstructive pulmonary disease and related phenotypes: an X chromosome-wide association study
Authors: Hayden Lystra P. , Hobbs Brian D. , Busch Robert , Cho Michael H. , Liu Ming , Lopes-Ramos Camila M. , Lomas David A. , Bakke Per , Gulsvik Amund , Silverman Edwin K. , Crapo James D. , Beaty Terri H. , Laird Nan M. , Lange Christoph , DeMeo Dawn L.
Published: February 2023

Background

The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations.

Methods

Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case–control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses.

Results

Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV1/FVC ($$\beta$$
β
0.020, SE 0.004, p 4.97 × 10–08), with suggestive evidence of association with FEV1 ($$\beta$$
β
0.092, SE 0.018, p 3.40 × 10–07). Sex-stratified analyses revealed X chromosome variants that were differentially trending in one sex, with significantly different effect sizes or directions.

Conclusions

This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology.

Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.
Environmental signals perceived by the brain abate pro-metastatic monocytes by dampening glucocorticoids receptor signaling
Authors: Canali María Magdalena , Guyot Mélanie , Simon Thomas , Daoudlarian Douglas , Chabry Joelle , Panzolini Clara , Petit-Paitel Agnès , Hypolite Nicolas , Nicolas Sarah , Bourdely Pierre , Schmid-Antomarchi Heidy , Schmid-Alliana Annie , Soria Javier , Karimdjee Soilihi Babou , Hofman Paul , Prevost-Blondel Armelle , Kato Masashi , Mougneau Evelyne , Glaichenhaus Nicolas , Blancou Philippe
Published: February 2023

While positive social-behavioral factors predict longer survival in cancer patients, the underlying mechanisms are unknown. Since tumor metastasis are the major cancer mortality factor, we investigated how an enriched environment (EE) conductive to enhanced sensory, cognitive and motor stimulation impact metastatic progression in lungs following intravasation in the circulation. We find that mice housed in EE exhibited reduced number of lung metastatic foci compared to control mice housed in a standard environment (SE). Compared to SE mice, EE mice increased lung inflammation as early as 4 days after circulating tumor cells extravasation. The impact of environmental signals on lung metastasis is independent of adrenergic receptors signaling. By contrast, we find that serum corticosterone levels are lower in EE mice and that glucocorticoid receptor (GR) antagonist reduces the number of lung metastasis in SE mice. In addition, the difference of the number of lung metastasis between SE and EE mice is abolished when inflammatory monocytes are rendered deficient in GR signaling. This decreased GR signaling in inflammatory monocytes of SE mice results in an exacerbated inflammatory profile in the lung. Our study shows that not only EE reduces late stages of metastatic progression in lungs but disclose a novel anti-tumor mechanism whereby GR-dependent reprogramming of inflammatory monocytes can inhibit metastatic progression in lungs. Moreover, while inflammatory monocytes have been shown to promote cancer progression, they also have an anti-tumor effect, suggesting that their role is more complex than currently thought.