bluuebunny/crossref_metadata_2025 huggingface dataset:
The contribution of Ca and Mg to the accumulation of amino acids in maize: from the response of physiological and biochemical processes
Authors: He Zhaoquan , Shang Xue , Wang Xiukang , Xing Yingying , Zhang Tonghui , Yun Jianying
Published: June 2024

Background

The quality of maize kernels is significantly enhanced by amino acids, which are the fundamental building blocks of proteins. Meanwhile, calcium (Ca) and magnesium (Mg), as important nutrients for maize growth, are vital in regulating the metabolic pathways and enzyme activities of amino acid synthesis. Therefore, our study analyzed the response process and changes of amino acid content, endogenous hormone content, and antioxidant enzyme activity in kernels to the coupling addition of sugar alcohol-chelated Ca and Mg fertilizers with spraying on maize.

Result

(1) The coupled addition of Ca and Mg fertilizers increased the Ca and Mg content, endogenous hormone components (indole-3-acetic acid, IAA; gibberellin, GA; zeatin riboside, ZR) content, antioxidant enzyme activity, and amino acid content of maize kernels. The content of Ca and Mg in kernels increased with the increasing levels of Ca and Mg fertilizers within a certain range from the filling to the wax ripening stage, and significantly positively correlated with antioxidant enzyme activities. (2) The contents of IAA, GA, and ZR continued to rise, and the activities of superoxide dismutase (SOD) and catalase (CAT) were elevated, which effectively enhanced the ability of cells to resist oxidative damage, promoted cell elongation and division, and facilitated the growth and development of maize. However, the malondialdehyde (MDA) content increased consistently, which would attack the defense system of the cell membrane plasma to some extent. (3) Leucine (LEU) exhibited the highest percentage of essential amino acid components and a gradual decline from the filling to the wax ripening stage, with the most substantial beneficial effect on essential amino acids. (4) CAT and SOD favorably governed essential amino acids, while IAA and MDA negatively regulated them. The dominant physiological driving pathway for the synthesis of essential amino acids was “IAA-CAT-LEU”, in which IAA first negatively drove CAT activity, and CAT then advantageously controlled LEU synthesis.

Conclusion

These findings provide a potential approach to the physiological and biochemical metabolism of amino acid synthesis, and the nutritional quality enhancement of maize kernel.
Age-specific differences in association of glycosylated hemoglobin levels with the prevalence of cardiovascular diseases among nondiabetics: the National Health and Nutrition Examination Survey 2005–2018
Authors: Fan Ruihan , Li Shuna , Xue Zihan , Yang Ruida , Lyu Jun , He Hairong
Published: June 2024

Background

Previous research has supported the presence of an association between high glycated hemoglobin (HbA1c) levels and cardiovascular disease (CVD). The objective of the present study was to determine whether increased HbA1c levels are associated with high CVD prevalence among nondiabetics. Furthermore, we aimed to explore the possible interaction of HbA1c levels and age in regard to CVD.

Methods

This cross-sectional study analyzed data of 28,534 adult participants in the National Health and Nutrition Examination Survey 2005–2018. The association between HbA1c and CVD was assessed using univariate and multivariate logistic regression models. Propensity score matching was used to reduce selection bias. Subgroup analysis and restricted cubic spline (RCS) were used to further characterize the association between HbA1c levels and CVD. We modeled additive interactions to further assess the relationship between HbA1c levels and age.

Results

In the multivariate logistic regression model, a positive association was found between CVD and increased HbA1c levels (highest quartile [Q4] vs. lowest quartile [Q1]: odds ratio [OR] = 1.277, 95% confidence interval [CI] = 1.111–1.469, P = 0.001). In the stratified analyses, the adjusted association between HbA1c and CVD was significant for those younger than 55 years (Q4 vs. Q1: OR = 1.437, 95% CI = 1.099–1.880, P = 0.008). RCS did not reveal a nonlinear relationship between HbA1c levels and CVD among nondiabetics (P for nonlinearity = 0.609). Additionally, a high HbA1c level was favorably connected with old age on CVD, with a synergistic impact.

Conclusions

Increased HbA1c levels were associated with high CVD prevalence among nondiabetics. However, we still need to carefully explain the effect of age on the relationship between HbA1c and CVD in nondiabetic population. Given the correlations of HbA1c with CVDs and CV events, HbA1c might be a useful indicator for predicting CVDs and CV events in the nondiabetic population.
Unusual Cutibacterium acnes splenic abscess with bacteremia in an immunocompetent man: phylotyping and clonal complex analysis
Authors: Roudeau Angèle , Corvec Stéphane , Heym Beate , d’Epenoux Louise Ruffier , Lidove Olivier , Zeller Valérie
Published: June 2024

Background

Cutibacterium acnes is an anaerobic bacterium mostly implicated in cutaneous and body-implant infections. Splenic abscess is a rare entity and C. acnes abscesses have only exceptionally been reported. We describe a spontaneous splenic C. acnes abscess in an immunocompetent man with no predisposing factors or identified portal of entry. His isolates were subjected to single-locus sequence typing (SLST) to explore their genetic relatedness and better understand this rare infection.

Case presentation

A splenic abscess was diagnosed on a computed-tomography scan in a 74-year-old man with chronic abdominal pain. No risk factor was identified. Abscess-drained pus and post-drainage blood cultures grew C. acnes. SLST of abscess and blood isolates showed that they belonged to the same C. acnes SLST type C1 found in normal skin and rarely in inflammatory skin disease. Specific virulence factors could not be identified.

Conclusion

C. acnes abscesses are extremely rare and can develop in immunocompetent patients without an identifiable portal of entry. Molecular typing of clinical isolates can help confirm infection (versus contamination) and enables genetic background comparisons. Further research is needed to understand C. acnes tropism and virulence.
Usefulness of the mini nutritional assessment short-form for evaluating nutritional status in patients with nontuberculous mycobacterial pulmonary disease: a prospective cross-sectional study
Authors: Chung Eunki , Park Youngmok , Lee Hye-Jeong , Kang Young Ae
Published: June 2024

Background

Although the Mini Nutritional Assessment (MNA) is recognized as a useful tool for evaluating nutritional status in patients with various diseases, its applicability in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) remains undetermined.

Methods

We designed a prospective cross-sectional study to investigate whether the MNA Short-Form (MNA-SF) score can serve as a screening tool to assess the nutritional status of patients with NTM-PD. The MNA-SF was conducted upon patient enrollment, and correlation analyses were performed to compare MNA-SF scores with other nutritional measurements and disease severity. Multivariable logistic regression analyses were conducted to evaluate the association between MNA-SF scores and NTM-PD severity.

Results

The 194 patients with NTM-PD included in the analysis had a median age of 65.0 (59.0–69.0) years; 59.3% (n = 115) had low MNA-SF scores (< 12). The low MNA-SF group exhibited a lower body mass index (19.7 vs. 22.4 kg/m2, p < 0.001) and fat-free mass index (14.7 vs. 15.6 kg/m2, p < 0.001) than the normal MNA-SF group, as well as higher incidences of sarcopenia (20.0% vs. 6.3%, p = 0.008) and adipopenia (35.7% vs. 5.1%, p < 0.001). However, no significant differences in calorie and protein intakes were observed between the two groups. Low MNA-SF scores were associated with radiographic severity (adjusted odds ratio 2.72, 95% confidence interval 1.38–5.36) but not with forced vital capacity.

Conclusions

The MNA-SF can effectively assess the nutritional status of patients with NTM-PD and can serve as an important clinical indicator in NTM-PD where treatment timing is determined by clinical judgment.
The elevated lactate dehydrogenase to albumin ratio is a risk factor for developing sepsis-associated acute kidney injury: a single-center retrospective study
Authors: Fang Yipeng , Zhang Yuan , Zhang Xin
Published: June 2024

Background

There is no evidence to determine the association between the lactate dehydrogenase to albumin ratio (LAR) and the development of sepsis-associated acute kidney injury (SAKI). We aimed to investigate the predictive impact of LAR for SAKI in patients with sepsis.

Methods

A total of 4,087 patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC IV) database were included. Logistic regression analysis was used to identify the association between LAR and the risk of developing SAKI, and the relationship was visualized using restricted cubic spline (RCS). The clinical predictive value of LAR was evaluated by ROC curve analysis. Subgroup analysis was used to search for interactive factors.

Results

The LAR level was markedly increased in the SAKI group (p < 0.001). There was a positive linear association between LAR and the risk of developing SAKI (p for nonlinearity = 0.867). Logistic regression analysis showed an independent predictive value of LAR for developing SAKI. The LAR had moderate clinical value, with an AUC of 0.644. Chronic kidney disease (CKD) was identified as an independent interactive factor. The predictive value of LAR for the development of SAKI disappeared in those with a history of CKD but remained in those without CKD.

Conclusions

Elevated LAR 12 h before and after the diagnosis of sepsis is an independent risk factor for the development of SAKI in patients with sepsis. Chronic comorbidities, especially the history of CKD, should be taken into account when using LAR to predict the development of AKI in patients with sepsis.
A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders
Authors: Husain Muhammad Omair , Jones Brett , Arshad Usman , Ameis Stephanie H. , Mirfallah Giselle , Schifani Christin , Rodak Terri , Aiken Madina , Shafique Mudassar , Ahmed Fatima , Voineskos Aristotle , Husain Muhammad Ishrat , Foussias George
Published: June 2024

Background

Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum.

Methods

PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment.

Results

Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003).

Conclusions

Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn.

PROSPERO

CRD42022359018.
Maternal depressive symptom trajectories and associations with child feeding
Authors: Fox Katelyn , Hart Chantelle N. , Phelan Suzanne , Ventura Alison K. , Wing Rena , Jelalian Elissa
Published: June 2024

Background

Responsive feeding, when caregivers attend to children’s signals of hunger and satiation and respond in an emotionally supportive and developmentally appropriate way, is associated with the development of healthy eating behaviors, improved diet quality, and healthy weight status for children. However, gaps in the literature remain on how factors, such as maternal depressive symptoms and child temperament, influence feeding interactions.

Methods

This longitudinal secondary data analysis explored the association between maternal depressive symptom trajectory and child temperament with maternal feeding practices in women with obesity who participated in a prenatal lifestyle intervention trial. Mothers self-reported depressive symptoms at baseline, 35 weeks gestation, and 6, 12, and 18 months postpartum. At 18- and 24-months postpartum, mothers completed self-reported assessments of feeding practices and child temperament and completed in-home video-recorded meals with their child, coded using the Responsiveness to Child Feeding Cues Scale. We used group-based trajectory modeling to identify distinct trajectories of depressive symptoms and generalized regressions to assess the association between symptom trajectory group and feeding. We also explored interactions between depressive symptoms and child temperament.

Results

Three distinct trajectories of depressive symptoms were identified: No-Minimal and Decreasing, Mild-Moderate and Stable, and Moderate-Severe and Stable. At 18-months, when compared to the No-Minimal and Decreasing group, membership in the Moderate-Severe and Stable group was associated with higher observed responsiveness to child satiation cues ($$B$$ =2.3, 95%CI = 0.2, 4.4) and lower self-reported pressure to eat ($$B$$=-0.4, 95%CI= -0.7, 0.0). When compared to the No-Minimal and Decreasing group, membership in the Mild-Moderate and Stable group was associated with higher self-reported restriction ($$B$$ =0.4, 95%CI = 0.0,0.7). The associations between trajectory group membership and feeding practices did not reach statistical significance at 24 months. Associations between depressive symptoms and restriction were moderated by child effortful control at 18 months $$(B=0.2, 95\% CI (0.0, 04)$$) and surgency at 24 months $$B=-0.3, 95\% CI (-0.6, 0.0)$$).

Conclusion

A Moderate-Severe and Stable depressive symptom trajectory was associated with more responsive feeding practices and a Mild-Moderate and Stable trajectory was associated with higher restrictive feeding. Preliminary evidence suggests that depressive symptoms impact mothers’ ability to match their use of restriction to the temperamental needs of their child.
Transgenic Arabidopsis thaliana plants expressing bacterial γ-hexachlorocyclohexane dehydrochlorinase LinA
Authors: Deng Wenhao , Takada Yoshinobu , Nanasato Yoshihiko , Kishida Kouhei , Stari Leonardo , Ohtsubo Yoshiyuki , Tabei Yutaka , Watanabe Masao , Nagata Yuji
Published: June 2024

Background

γ-Hexachlorocyclohexane (γ-HCH), an organochlorine insecticide of anthropogenic origin, is a persistent organic pollutant (POP) that causes environmental pollution concerns worldwide. Although many γ-HCH-degrading bacterial strains are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the low survival rate of the exogenous bacteria. Another strategy for the bioremediation of γ-HCH involves the use of transgenic plants expressing bacterial enzyme for γ-HCH degradation through phytoremediation.

Results

We generated transgenic Arabidopsis thaliana expressing γ-HCH dehydrochlroninase LinA from bacterium Sphingobium japonicum strain UT26. Among the transgenic Arabidopsis T2 lines, we obtained one line (A5) that expressed and accumulated LinA well. The A5-derived T3 plants showed higher tolerance to γ-HCH than the non-transformant control plants, indicating that γ-HCH is toxic for Arabidopsis thaliana and that this effect is relieved by LinA expression. The crude extract of the A5 plants showed γ-HCH degradation activity, and metabolites of γ-HCH produced by the LinA reaction were detected in the assay solution, indicating that the A5 plants accumulated the active LinA protein. In some A5 lines, the whole plant absorbed and degraded more than 99% of γ-HCH (10 ppm) in the liquid medium within 36 h.

Conclusion

The transgenic Arabidopsis expressing active LinA absorbed and degraded γ-HCH in the liquid medium, indicating the high potential of LinA-expressing transgenic plants for the phytoremediation of environmental γ-HCH. This study marks a crucial step toward the practical use of transgenic plants for the phytoremediation of POPs.
CONSORT statement adherence and risk of bias in randomized controlled trials on deep caries management: a meta-research
Authors: Elagami Rokaia Ahmed , Reis Thais Marchezini , Hassan Mohamed Ahmed , Tedesco Tamara Kerber , Braga Mariana Minatel , Mendes Fausto Medeiros , Cenci Maximiliano Sérgio , Huysmans Marie-Charlotte , Raggio Daniela Prócida
Published: June 2024

Background

Recently, trials have supported changes in deep caries management. However, reporting might lack details, affecting interpretation and implementation. Thus, we aimed to evaluate the adherence to the CONSORT statement and the risk of bias of randomized controlled trials (RCTs) on deep caries management published in pediatric dental journals.

Methods

We searched PubMed for RCTs in six pediatric dental journals between 2010 and 2022, focusing on deep caries lesion management. Adherence to the CONSORT guideline and the risk of bias were assessed using a modified tool with 19 items; each scored from 0 to 2 (maximum of 38 points), and the Cochrane risk-of-bias (RoB 2) tool. We performed descriptive and regression analyses (α = 5%).

Results

We analyzed 127 RCTs. The mean (standard deviation) CONSORT adherence score was 21.1 (6.7). Notably, 96.1% of the studies received a score of 2 for the "intervention" item, whereas 83.5% scored 0 for the "estimated effect size”. The risk of bias assessment revealed that 40.2% of the RCTs were at high risk, 59% were at low risk, and 0.8% were at low risk. RCTs with a high risk of bias had lower CONSORT scores (p<0.001) than those with low or some concerns. RCTs published in journals without the endorsement of the CONSORT statement had lower scores than those in journals with the endorsement of the CONSORT statement. Older RCTs (6-10 years old and more than 10 years old) showed significantly lower CONSORT statement compliance than trials published recently within 5 years.

Conclusion

Adherence to the CONSORT was relatively low among the investigated RCTs. Moreover, lower adherence to the CONSORT was associated with a higher risk of bias.

Trial Registration

This study protocol was prospectively registered on the Open Science Framework - DOI (10.17605/OSF.IO/V6SYZ).
Comparison of perineural and systemic dexamethasone use in impacted third molar surgeries in terms of anesthesia duration and postoperative complaints: a controlled, randomized observational study
Authors: Kaya Doğan Ilgaz , Aktı Ahmet
Published: June 2024

Background

Surgical extraction of impacted third molars (ITM) often leads to postoperative discomfort including pain, swelling, and limited function. Steroids like dexamethasone (DXN) are commonly used in oral surgery to manage pain and inflammation. Various administration routes for DXN exist, including intravenous (IV), perineural (PN), and oral applications, each with its advantages. Previous studies have shown that adding DXN to local anesthetics can prolong anesthesia duration and reduce postoperative sequelae. However, comparative studies on IV and PN applications with inferior alveolar nerve block (IANB) of DXN in ITM surgeries are limited.

Methods

This controlled, randomized observational study involved patients undergoing Class II position B ITM extraction. Patients were divided into three groups. IANB (1.8 ml of articaine hydrochloride + 1 ml of saline) was performed 1 h after IV-DXN (4 mg/ml DXN) was administered to the IV group. DXN along with IANB (1.8 ml of articaine hydrochloride + 1 ml of 4 mg/ml DXN) was applied to the PN group. Only IANB (1.8 ml of articaine hydrochloride + 1 ml of saline) was applied to the control group. Anesthesia duration was assessed as primary outcomes. Anesthesia duration was evaluated using a vitalometer from the molars. Secondary outcomes included postoperative pain and edema measured on the 1st, 3rd, and 7th days after surgery. Pain was evaluated postoperatively by using a visual analog scale. A p-value < 0.05 was considered statistically significant.

Results

The study included 45 patients with similar demographic characteristics across groups. IV application significantly prolonged anesthesia duration compared to the control group. (p = 0.049) Both IV and PN administration of DXN reduced postoperative edema at 3rd (p = 0.048) and 7th day (p = 0.01). Post-procedure pain reduction was significant in the IV group (p = 0.011). On the other hand, it was observed that the pain did not decrease in the PN group at 3rd and 7th days compared to the control and IV groups.

Conclusions

PN and IV DXN administration prolonged anesthesia duration and reduced postoperative edema in ITM surgeries. However, PN DXN administration was associated with increased postoperative pain compared to IV DXN and control groups. Further studies comparing different doses and administration routes of DXN are needed to determine optimal strategies for managing postoperative discomfort in ITM surgeries.

Trial registration

This study was conducted at Ahmet Keleşoğlu Faculty of Dentistry with the permission of Karamanoğlu Mehmetbey University Faculty of Medicine Ethics Committee (#04-2022/101). Trial registration is also available at clinicaltrail.gov. (NCT06318013, 26/05/2024)
Exploring lived experiences on the usage of removable complete dentures among edentulous patients attending Makerere University Dental Hospital, Kampala, Uganda
Authors: Nono David , Bagenda Godfrey , Okullo Isaac , Rwenyonyi Charles Mugisha
Published: June 2024

Background

Edentulism remains a major disability worldwide, especially among the elderly population, although the prevalence of complete edentulism has declined over the last decades. In Uganda, the prevalence of edentulism in people aged 20 years and above is 1.8%. The therapy for edentulous patients can be realized through the use of conventional removable complete dentures, implant-supported prostheses, and computer-aided design and computer-aided manufacturing (CADCAM), however, the provision of removable complete dentures continues to be the predominant rehabilitation for edentulous patients. However, no published study has explored the lived experiences with removable complete dentures among the Ugandan population. The aim of the present study was to explore patients’ lived experiences on the usage of removable complete dentures among Ugandan edentulous patients attending Makerere University Dental Hospital.

Methods

This was a qualitative study approach using purposive sampling. Fifteen (15) respondents were selected across social demographics. Interviews were recorded and transcribed and themes were generated to draw a deeper meaning to the usage of removable complete dentures. A qualitative statistical package, Atlas Ti software was used to generate themes from the interviews followed by an interpretation of the generated data and the results were presented as text and in a table.

Results

The reported key positive experiences due to removable complete denture rehabilitation were the improvement in speech, eating ability, regaining good facial appearance, better oral hygiene management, self-esteem and confidence to smile in public, and a feeling of completeness. However, respondents complained of pain and discomfort due to the looseness of dentures, inability to eat certain foods, and regular cleaning of dentures. The respondents did not go through proper informed consent processes before getting removable complete dentures.

Conclusion

The study found that patients were satisfied with their removable complete dentures rehabilitation due to the positive experiences registered, such as the ability to eat and talk well, and restoration of self-esteem, all of which improved their quality of life. However, they experience pain and discomfort due to the looseness of dentures.
Patient, supporter and primary healthcare professional perspectives on health risks in over 16s with attention deficit hyperactivity disorder (ADHD) in England: a national survey study
Authors: Ward John H. , Becker Kieran , Smith Jane , Price Anna , Newlove-Delgado Tamsin
Published: June 2024

Background

Current research suggests that people with attention deficit hyperactivity disorder (ADHD) are at higher risk of physical and mental health disorders. This study aimed to explore these health risks in ADHD from the perspectives of multiple stakeholders.

Methods

This study forms part of the ‘Managing young people with ADHD in Primary care (MAP) study’. A survey developed by the study team was distributed to over 16 year olds with ADHD, their supporters, primary healthcare professionals and health commissioners across England, via social media and through patient/clinical networks (September—October 2022). This survey contained two questions on health risks. Question one asked about views on health risks in ADHD (free text). Question two asked about advice given (options list and free text). Descriptive statistics summarised responses to questions one and two, and qualitative analysis (reflexive thematic analysis) was used to explore free text responses from question one.

Results

782 participants responded to the MAP survey. Of these, 206 healthcare professionals, 157 people with ADHD and 88 supporters answered question one. The most mentioned perceived risks were substance misuse, sleep disorders, weight management and smoking. More people with ADHD reported disordered eating as a health risk (n = 32) than healthcare professionals (n = 5). Generated themes included perceived health risks, impact of living with ADHD, lack of adequate healthcare, and need for ADHD awareness. In respect to advice given (question two), based on responses from 258 professionals, 162 people with ADHD and 100 supporters, the most common advice discussed in consultation was mental health (n = 149, n = 50 and n = 17 respectively). High numbers of respondents reported not giving/receiving advice on wider health (n = 38, n = 88 and n = 61 respectively).

Conclusions

Findings demonstrate that respondents perceived a range of physical and mental health risks posed by ADHD. These related to difficulties with activities of daily living, as well as healthcare interactions and the impact of core features of ADHD (e.g. impulsivity, emotional dysregulation). These risks are not currently explicitly addressed in United Kingdom national guidance on ADHD. More work is needed to examine and address the broader health outcomes of people with ADHD.
Clinical, imaging and histopathological characterization of a series of three cats with cerebellar cortical degeneration
Authors: Giron Céline , Hélie Pierre , Parent Joane , Boutin Mathieu , St-Jean Guillaume
Published: June 2024

Background

Neurological inherited disorders are rare in domestic animals. Cerebellar cortical degeneration remains amongst the most common of these disorders. The condition is defined as the premature loss of fully differentiated cerebellar components due to genetic or metabolic defects. It has been studied in dogs and cats, and various genetic defects and diagnostic tests (including magnetic resonance imaging (MRI)) have been refined in these species. Cases in cats remain rare and mostly individual, and few diagnostic criteria, other than post-mortem exam, have been evaluated in reports with multiple cases. Here, we report three feline cases of cerebellar cortical degeneration with detailed clinical, diagnostic imaging and post-mortem findings.

Case presentation

The three cases were directly (siblings, case #1 and #2) or indirectly related (same farm, case #3) and showed early-onset of the disease, with clinical signs including cerebellar ataxia and tremors. Brain MRI was highly suggestive of cerebellar cortical degeneration on all three cases. The relative cerebrospinal fluid (CSF) space, relative cerebellum size, brainstem: cerebellum area ratio, and cerebellum: total brain area ratio, were measured and compared to a control group of cats and reference cut-offs for dogs in the literature. For the relative cerebellum size and cerebellum: total brain area ratio, all affected cases had a lower value than the control group. For the relative CSF space and brainstem: cerebellum area ratio, the more affected cases (#2 and #3) had higher values than the control group, while the least affected case (#3) had values within the ranges of the control group, but a progression was visible over time. Post-mortem examination confirmed the diagnosis of cerebellar cortical degeneration, with marked to complete loss of Purkinje cells and associated granular layer depletion and proliferation of Bergmann glia. One case also had Wallerian-like degeneration in the spinal cord, suggestive of spinocerebellar degeneration.

Conclusion

Our report further supports a potential genetic component for the disease in cats. For the MRI examination, the relative cerebellum size and cerebellum: total brain area ratio seem promising, but further studies are needed to establish specific feline cut-offs. Post-mortem evaluation of the cerebellum remains the gold standard for the final diagnosis.
Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study
Authors: Vlacho Bogdan , Bundó Magdalena , Llussà Judit , Real Jordi , Mata-Cases Manel , Cos Xavier , Tundidor Diana , Zaccardi Francesco , Khunti Kamlesh , Jude Edward B. , Franch-Nadal Josep , Mauricio Dídac
Published: June 2024

Background

To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings.

Methods

We built a cohort of people with a first DFD episode during 2010–2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events.

Results

Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7–22.6, HR: 15.1, 95% CI: 13.8–16.5, respectively) was found.

Conclusions

Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.

Graphical Abstract
Assessing CRISPR/Cas9 potential in SDG3 attainment: malaria elimination—regulatory and community engagement landscape
Authors: Snuzik Aleksandra
Published: June 2024

Elimination of malaria has become a United Nations member states target: Target 3.3 of the sustainable development goal no. 3 (SDG3). Despite the measures taken, the attainment of this goal is jeopardized by an alarming trend of increasing malaria case incidence. Globally, there were an estimated 241 million malaria cases in 2020 in 85 malaria-endemic countries, increasing from 227 million in 2019. Malaria case incidence was 59, which means effectively no changes in the numbers occurred, compared with the baseline 2015. Jennifer Doudna—co-inventor of CRISPR/Cas9 technology—claims that CRISPR holds the potential to lessen or even eradicate problems lying in the centre of SDGs. On the same note, CRISPR/Cas9-mediated mosquito-targeting gene drives (MGD) are perceived as a potential means to turn this trend back and put momentum into the malaria elimination effort. This paper assessed two of the critical elements of the World Health Organization Genetically modified mosquitoes (WHO GMM) Critical Pathway framework: the community and stakeholders’ engagement (inability to employ widely used frameworks, segmentation of the public, ‘bystander’ status, and guidelines operationalization) and the regulatory landscape (lex generali, ‘goldilocks dilemma’, and mode of regulation) concerning mosquito-oriented gene drives (MGD) advances. Based on the assessment findings, the author believes that CRISPR/Cas-9-mediated MGD will not contribute to the attainment of SDG3 (Target 3.3), despite the undisputable technology’s potential. This research pertains to the state of knowledge, legal frameworks, and legislature, as of November 2022.
SHH induces macrophage oxidative phosphorylation and efferocytosis to promote scar formation
Authors: Zhang Julei , He Zeliang , Xiong Chenlu , Yao Yuanyuan , Zhang Chengliang , Yao Wende , Yang Sihan , Li Xiaodong , Han Yan
Published: June 2024

Excessive scar formation such as hypertrophic scars and keloids, resulting from trauma or surgical procedures, present a widespread concern for causing disfigurement, discomfort, and functional limitations. Macrophages play pivotal roles in maintaining tissue homeostasis, orchestrating tissue development, repair, and immune responses, and its transition of function and phenotype plays a critical role in regulating the balance between inflammation and tissue regeneration, which is central to cutaneous scar formation. Recent evidence suggests the involvement of Sonic Hedgehog (SHH) in the induction of anti-inflammatory M2-like macrophage phenotypes within tumor microenvironments. In our study, we observed increased SHH expression in human hypertrophic scars, prompting an investigation into its influence on macrophage polarization, efferocytosis, and cutaneous scar formation. Our findings reveal that SHH can enhance oxidative phosphorylation (OXPHOS) in macrophages, augment macrophage efferocytosis, and promote M2 polarization, finally contributing to the progression of cutaneous scar formation. Notably, targeting SHH signaling with vismodegib exhibited promising potential in mitigating scar formation by reversing the effects of enhanced OXPHOS and M2 polarization in macrophages. In conclusion, this study underscores the critical roles of macrophage metabolism, particularly OXPHOS, efferocytosis and SHH signaling in cutaneous scar formation. Understanding these mechanisms provides new avenues for potential interventions and scar prevention strategies.
Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer
Authors: Wang Jiajia , Liu Hui , Yu Zeyuan , Zhou Qianqian , Sun Feifei , Han Jingying , Gao Lin , Dou Baokai , Zhang Hanwen , Fu Jiawei , Jia Wenqiao , Chen Weiwen , Hu Jing , Han Bo
Published: June 2024

Background

Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors.

Methods

Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth.

Results

RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa.

Conclusion

In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.
Transcriptome analysis identifies an ASD-Like phenotype in oligodendrocytes and microglia from C58/J amygdala that is dependent on sex and sociability
Authors: Dalton George D. , Siecinski Stephen K. , Nikolova Viktoriya D. , Cofer Gary P. , Hornburg Kathryn J. , Qi Yi , Johnson G. Allan , Jiang Yong-Hui , Moy Sheryl S. , Gregory Simon G.
Published: June 2024

Background

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model.

Methods

Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala.

Results

C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin’s beneficial effects on myelin gene expression.

Limitations

Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin’s effects need further examination to understand its’ potential as an ASD therapeutic.

Conclusions

Our work demonstrates the C58/J mouse model’s utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.
Risk factors for subsequent suicidal acts among 12–25-year-old high-risk callers to a suicide prevention hotline in China: a longitudinal study
Authors: Wu Jianlan , Zhang Ruoyun , Zhao Liting , Yin Yi , Min Jing , Ge Yiming , Luo Yang , Li Peiyao , Li Lingling , Tong Yongsheng
Published: June 2024

Background

A few previous cross-sectional studies investigated correlated factors of suicidal ideation or suicide attempts among suicide prevention hotline callers; however, scarcely any evidence was from a longitudinal study. In addition, it is still unclear whether improvements in some suicide risk factors could reduce the occurrence of subsequent suicidal acts. This longitudinal study focusing on the risk factors for subsequent suicidal acts among adolescent and young adult callers with high suicide risk aims to fill this gap.

Methods

This study recruited 12–25-year-old high-risk callers to a China nationwide suicide prevention hotline. Potential risk factors, including hopefulness, psychological distress, depression, history of suicide attempts, alcohol or substance misuse, and acute life events, were examined during the index calls, and improvements in hopefulness, psychological distress, and suicide intent were assessed before ending the index calls. The recruited callers were followed up 12 months after their index calls. The primary outcome was the occurrence of suicidal acts (suicide attempts or suicide death) during follow-up. Kaplan–Meier survival curves, log-rank tests, and Cox proportional hazards model were used.

Results

During the follow-up period, 271 of 1656 high-risk adolescent and young adult callers attempted suicide, and seven callers died by suicide. After adjusting for demographic variables, low hopefulness (Hazard Ratio [HR] = 2.03, 95% Confidence Interval [CI]=[1.47, 2.80]) at the beginning of the index call was associated with a higher risk for subsequent suicidal acts, whereas improvements in psychological distress (HR = 0.61, 95%CI [0.41, 0.89]) and suicidal intent (HR = 0.56, 95%CI [0.38, 0.84]) during the index call reduced the risk of subsequent suicidal acts. In addition, alcohol or substance misuse (Model 2, HR = 1.65, 95%CI [1.11, 2.46]) and suicide attempt history(Model 1: one episode, HR = 1.96, 95%CI=[1.05, 3.66]; two or more episodes, HR = 2.81, 95%CI [1.59, 4.96]. Model 2: one episode, HR = 2.26, 95%CI [1.06, 4.82]; two or more episodes: HR = 3.28, 95%CI [1.63, 6.60]) were risk factors for subsequent suicidal acts.

Conclusions

While suicide prevention hotline operators deliver brief psychological interventions to high-risk adolescent and young adult callers, priority should be given to callers with low hopefulness and to the alleviation of callers’ high psychological distress and suicide intent.
An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs
Authors: Chapple Richard H. , Liu Xueying , Natarajan Sivaraman , Alexander Margaret I. M. , Kim Yuna , Patel Anand G. , LaFlamme Christy W. , Pan Min , Wright William C. , Lee Hyeong-Min , Zhang Yinwen , Lu Meifen , Koo Selene C. , Long Courtney , Harper John , Savage Chandra , Johnson Melissa D. , Confer Thomas , Akers Walter J. , Dyer Michael A. , Sheppard Heather , Easton John , Geeleher Paul
Published: June 2024

Background

Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models.

Results

Here, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We develop an unsupervised machine learning approach (“automatic consensus nonnegative matrix factorization” (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirm a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly, however, this weak-mesenchymal-like program is maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 h, suggesting an uncharacterized therapy-escape mechanism.

Conclusions

Collectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets.