bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying opportunities for prevention of adverse outcomes following female genital fistula repair: protocol for a mixed-methods study in Uganda
Authors: El Ayadi Alison M. , Obore Susan , Kirya Fred , Miller Suellen , Korn Abner , Nalubwama Hadija , Neuhaus John , Getahun Monica , Eyul Patrick , Twine Robert , Andrew Erin V. W. , Barageine Justus K.
Published: January 2024

Background

Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify these adverse risks and inform clinical and counseling interventions to optimize women’s health and quality of life following fistula repair through: identifying predictors and characteristics of post-repair fistula breakdown and recurrence (Objective 1) and post-repair incontinence (Objective 2), and to identify feasible and acceptable intervention strategies (Objective 3).

Methods

This mixed-methods study incorporates a prospective cohort of women with successful vesicovaginal fistula repair at approximately 12 fistula repair centers in Uganda (Objectives 1-2) followed by qualitative inquiry among key stakeholders (Objective 3). Cohort participants will have a baseline visit at the time of surgery followed by data collection at 2 weeks, 6 weeks, 3 months and quarterly thereafter for 3 years. Primary predictors to be evaluated include patient-related factors, fistula-related factors, fistula repair-related factors, and post-repair behaviors and exposures, collected via structured questionnaire at all data collection points. Clinical exams will be conducted at baseline, 2 weeks post-surgery, and for outcome confirmation at symptom development. Primary outcomes are fistula repair breakdown or fistula recurrence and post-repair incontinence. In-depth interviews will be conducted with cohort participants (n ~ 40) and other key stakeholders (~ 40 including family, peers, community members and clinical/social service providers) to inform feasibility and acceptability of recommendations.

Discussion

Participant recruitment is underway. This study is expected to identify key predictors that can directly improve fistula repair and post-repair programs and women’s outcomes, optimizing health and quality of life. Furthermore, our study will create a comprehensive longitudinal dataset capable of supporting broad inquiry into post-fistula repair health.

Trial Registration ClinicalTrials.gov Identifier: NCT05437939.
Chronic COVID-19 infection in an immunosuppressed patient shows changes in lineage over time: a case report
Authors: Baker Sheridan J. C. , Nfonsam Landry E. , Leto Daniela , Rutherford Candy , Smieja Marek , McArthur Andrew G.
Published: January 2024

Background

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 virus, emerged in late 2019 and spready globally. Many effects of infection with this pathogen are still unknown, with both chronic and repeated COVID-19 infection producing novel pathologies.

Case presentation

An immunocompromised patient presented with chronic COVID-19 infection. The patient had history of Hodgkin’s lymphoma, treated with chemotherapy and stem cell transplant. During the course of their treatment, eleven respiratory samples from the patient were analyzed by whole-genome sequencing followed by lineage identification. Whole-genome sequencing of the virus present in the patient over time revealed that the patient at various timepoints harboured three different lineages of the virus. The patient was initially infected with the B.1.1.176 lineage before coinfection with BA.1. When the patient was coinfected with both B.1.1.176 and BA.1, the viral populations were found in approximately equal proportions within the patient based on sequencing read abundance. Upon further sampling, the lineage present within the patient during the final two timepoints was found to be BA.2.9. The patient eventually developed respiratory failure and died.

Conclusions

This case study shows an example of the changes that can happen within an immunocompromised patient who is infected with COVID-19 multiple times. Furthermore, this case demonstrates how simultaneous coinfection with two lineages of COVID-19 can lead to unclear lineage assignment by standard methods, which are resolved by further investigation. When analyzing chronic COVID-19 infection and reinfection cases, care must be taken to properly identify the lineages of the virus present.
Sex, hormones and cerebrovascular function: from development to disorder
Authors: Collignon Adeline , Dion-Albert Laurence , Ménard Caroline , Coelho-Santos Vanessa
Published: January 2024

Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood–brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis.

Sex hormonal dysregulation in early development has been implicated in neurodevelopmental disorders with highly sexually dimorphic features, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Both disorders show higher prevalence in men, with varying symptoms between sexes, with boys exhibiting more externalizing behaviors, such as aggressivity or hyperactivity, and girls displaying higher internalizing behaviors, including anxiety, depression, or attention disorders. Indeed, ASD and ADHD are linked to high prenatal testosterone exposure and reduced aromatase expression, potentially explaining sex differences in prevalence and symptomatology. In line with this, high estrogen levels seem to attenuate ADHD symptoms. At the cerebrovascular level, sex- and region-specific variations of cerebral blood flow perfusion have been reported in both conditions, indicating an impact of gonadal hormones on the brain vascular system, disrupting its ability to respond to neuronal demands.

This review aims to provide an overview of the existing knowledge concerning the impact of sex hormones on cerebrovascular formation and maturation, as well as the onset of neurodevelopmental disorders. Here, we explore the concept of gonadal hormone interactions with brain vascular and BBB development to function, with a particular focus on the modulation of VEGF and Wnt signaling. We outline how these pathways may be involved in the underpinnings of ASD and ADHD. Outstanding questions and potential avenues for future research are highlighted, as uncovering sex-specific physiological and pathological aspects of brain vascular development might lead to innovative therapeutic approaches in the context of ASD, ADHD and beyond.
A risk model based on 10 ferroptosis regulators and markers established by LASSO-regularized linear Cox regression has a good prognostic value for ovarian cancer patients
Authors: Xiong Tingchuan , Wang Yinghong , Zhu Changjun
Published: January 2024

Ovarian cancer is the deadliest gynecologic cancer due to its high rate of recurrence and limited early diagnosis. For certain patients, particularly those with recurring disorders, standard treatment alone is insufficient in the majority of cases. Ferroptosis, an iron- and ROS (reactive oxygen species)-reliant cell death, plays a vital role in the occurrence of ovarian cancer. Herein, subjects from TCGA-OV were calculated for immune scores using the ESTIMATE algorithm and assigned into high- (N = 185) or low-immune (N = 193) score groups; 259 ferroptosis regulators and markers were analyzed for expression, and 64 were significantly differentially expressed between two groups. These 64 differentially expressed genes were applied for LASSO-regularized linear Cox regression for establishing ferroptosis regulators and a markers-based risk model, and a 10-gene signature was established. The ROC curve indicated that the risk score-based curve showed satisfactory predictive efficiency. Univariate and multivariate Cox risk regression analyses showed that age and risk score were risk factors for ovarian cancer patients’ overall survival; patients in the high-risk score group obtained lower immune scores. The Nomogram analysis indicated that the model has a good prognostic performance. GO functional enrichment annotation confirmed again the involvement of these 10 genes in ferroptosis and immune activities. TIMER online analysis showed that risk factors and immune cells were significantly correlated. In conclusion, the risk model based on 10 ferroptosis regulators and markers has a good prognostic value for ovarian cancer patients.
High-expressed ACAT2 predicted the poor prognosis of platinum-resistant epithelial ovarian cancer
Authors: Wang Jinfeng , Yang Zhe , Bai Han , Zhao Lanbo , Ji Jing , Bin Yadi , Liu Yu , Zhang Siyi , Hou Huilian , Li Qiling
Published: January 2024

Background

Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC).

Methods

ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models.

Results

ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15–4.11, P = 0.017) affected OS independently, rather than PFI and PFS.

Conclusion

The expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.
Hyperthermic intraperitoneal chemotherapy in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei: a 10-year treatment experience in China
Authors: Wang Bing , Ma Ruiqing , Shi Guanjun , Fan Xiwen , Rao Benqiang , Xu Hongbin
Published: January 2024

Background

To explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei (PMP).

Methods

We retrospectively analyzed the clinical data of 526 patients with incomplete cytoreduction for appendiceal PMP to discover its prognostic factors, and the therapeutic value of HIPEC.

Results

The 5-year and 10-year overall survival rates of patients after cytoreductive surgery (CRS) treated with HIPEC were significantly higher than those without HIPEC (5y-OS: 58% vs. 48%, 10y-OS: 37% vs. 16%, P = 0.032). The median progression-free survival (PFS) following CRS was 20 months, with a 20% 3-year PFS. The median PFS following CRS + HIPEC was 33 months, with a 60% 3-year PFS (P = 0.000). Univariate analysis indicated that HIPEC, gender, completeness of cytoreduction (CCR) and pathological grade had statistical difference. Multivariate analysis showed that CRS without HIPEC and high pathological grade were independent risk factors for poor prognosis and rapid tumor progression.

Conclusions

HIPEC may prolong the survival in patients with incomplete cytoreduction for low-grade appendiceal PMP. High pathological grade indicates poor survival and rapid tumor progression.
Protocol of a monocentric, double-blind, randomized, superiority, controlled trial evaluating the effect of in-prison OROS-methylphenidate vs. placebo treatment in detained people with attention-deficit hyperactivity disorder (BATIR)
Authors: Baggio Stéphanie , Billieux Joël , Dirkzwager Anja , Iglesias Katia , Moschetti Karine , Perroud Nader , Schneider Marie , Vernaz Nathalie , Wolff Hans , Heller Patrick
Published: January 2024

Background

Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes.

Methods

This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis).

Discussion

We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release.

Trial registration

ClinicalTrials.govNCT05842330. Registered on June 5, 2023.

Kofam.ch SNCTP000005388. Registered on July 17, 2023.
Microfluidic PCR and network analysis reveals complex tick-borne pathogen interactions in the tropics
Authors: Díaz-Corona Cristian , Roblejo-Arias Lisset , Piloto-Sardiñas Elianne , Díaz-Sánchez Adrian A. , Foucault-Simonin Angélique , Galon Clemence , Wu-Chuang Alejandra , Mateos-Hernández Lourdes , Zając Zbigniew , Kulisz Joanna , Wozniak Aneta , Castro-Montes de Oca María Karla , Lobo-Rivero Evelyn , Obregón Dasiel , Moutailler Sara , Corona-González Belkis , Cabezas-Cruz Alejandro
Published: January 2024

Background

Ixodid ticks, particularly Rhipicephalus sanguineus s.l., are important vectors of various disease-causing agents in dogs and humans in Cuba. However, our understading of interactions among tick-borne pathogens (TBPs) in infected dogs or the vector R. sanguineus s.l. remains limited. This study integrates microfluidic-based high-throughput real-time PCR data, Yule's Q statistic, and network analysis to elucidate pathogen-pathogen interactions in dogs and ticks in tropical western Cuba.

Methods

A cross-sectional study involving 46 client-owned dogs was conducted. Blood samples were collected from these dogs, and ticks infesting the same dogs were morphologically and molecularly identified. Nucleic acids were extracted from both canine blood and tick samples. Microfluidic-based high-throughput real-time PCR was employed to detect 25 bacterial species, 10 parasite species, 6 bacterial genera, and 4 parasite taxa, as well as to confirm the identity of the collected ticks. Validation was performed through end-point PCR assays and DNA sequencing analysis. Yule's Q statistic and network analysis were used to analyse the associations between different TBP species based on binary presence-absence data.

Results

The study revealed a high prevalence of TBPs in both dogs and R. sanguineus s.l., the only tick species found on the dogs. Hepatozoon canis and Ehrlichia canis were among the most common pathogens detected. Co-infections were observed, notably between E. canis and H. canis. Significant correlations were found between the presence of Anaplasma platys and H. canis in both dogs and ticks. A complex co-occurrence network among haemoparasite species was identified, highlighting potential facilitative and inhibitory roles. Notably, H. canis was found as a highly interconnected node, exhibiting significant positive associations with various taxa, including A. platys, and E. canis, suggesting facilitative interactions among these pathogens. Phylogenetic analysis showed genetic diversity in the detected TBPs.

Conclusions

Overall, this research enhances our understanding of TBPs in Cuba, providing insights into their prevalence, associations, and genetic diversity, with implications for disease surveillance and management.

Graphical abstract
The impact of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr long-lasting insecticidal nets on density of primary malaria vectors Anopheles gambiae s.s. and Anopheles coluzzii in Benin: a secondary analysis of a cluster randomised controlled trial
Authors: Yovogan Boulais , Sovi Arthur , Djènontin Armel , Adoha Constantin J. , Akinro Bruno , Accrombessi Manfred , Dangbénon Edouard , Koukpo Come Z. , Affolabi Zul-Kifl , Agboho Prudenciène A. , Kpanou Casimir Dossou , Assongba Landry , Missihoun Antoine Abel , Tokponnon Tatchémè Filémon , Agbangla Clément , Padonou Germain Gil , Messenger Louisa A. , Ngufor Corine , Cook Jackie , Akogbéto Martin C. , Protopopoff Natacha
Published: January 2024

Background

Long-lasting insecticidal nets (LLINs) may have different impacts on distinct mosquito vector species. We assessed the efficacy of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr LLINs on the density of Anopheles gambiae s.s. and An. coluzzii compared to pyrethroid-only nets in a three-arm cluster randomised control trial in Benin.

Methods

Indoor and outdoor collections of adult mosquitoes took place in 60 clusters using human landing catches at baseline and every 3 months for 2 years. After morphological identification, around 15% of randomly selected samples of An. gambiae s.l. were dissected to determine parity, species (using PCR).

Results

Overall, a total of 46,613 mosquito specimens were collected at baseline and 259,250 in the eight quarterly collections post-net distribution. Post-net distribution, approximately 70% of the specimens of An. gambiae s.l. speciated were An. coluzzii, while the rest were mostly composed of An. gambiae s.s. with a small proportion (< 1%) of hybrids (An. gambiae/coluzzii). There was no evidence of a significant reduction in vector density indoors in either primary vector species [An. coluzzii: DR (density ratio) = 0.62 (95% CI 0.21–1.77), p = 0.3683 for the pyrethroid-pyriproxyfen LLIN and DR = 0.56 (95% CI 0.19–1.62), p = 0.2866 for the pyrethroid-chlorfenapyr LLIN, An. gambiae s.s.: DR = 0.52 (95% CI 0.18–1.46), p = 0.2192 for the pyrethroid-pyriproxyfen LLIN and DR = 0.53 (95% CI 0.19–1.46), p = 0.2222 for the pyrethroid-chlorfenapyr]. The same trend was observed outdoors. Parity rates of An. gambiae s.l. were also similar across study arms.

Conclusions

Compared with pyrethroid-only LLINs, pyrethroid-chlorfenapyr LLINs and pyrethroid-pyriproxyfen LLINs performed similarly against the two primary mosquito species An. gambiae s.s. and An. coluzzii in Benin.

Graphical Abstract
Using multi-scale genomics to associate poorly annotated genes with rare diseases
Authors: Canavati Christina , Sherill-Rofe Dana , Kamal Lara , Bloch Idit , Zahdeh Fouad , Sharon Elad , Terespolsky Batel , Allan Islam Abu , Rabie Grace , Kawas Mariana , Kassem Hanin , Avraham Karen B. , Renbaum Paul , Levy-Lahad Ephrat , Kanaan Moien , Tabach Yuval
Published: January 2024

Background

Next-generation sequencing (NGS) has significantly transformed the landscape of identifying disease-causing genes associated with genetic disorders. However, a substantial portion of sequenced patients remains undiagnosed. This may be attributed not only to the challenges posed by harder-to-detect variants, such as non-coding and structural variations but also to the existence of variants in genes not previously associated with the patient’s clinical phenotype. This study introduces EvORanker, an algorithm that integrates unbiased data from 1,028 eukaryotic genomes to link mutated genes to clinical phenotypes.

Methods

EvORanker utilizes clinical data, multi-scale phylogenetic profiling, and other omics data to prioritize disease-associated genes. It was evaluated on solved exomes and simulated genomes, compared with existing methods, and applied to 6260 knockout genes with mouse phenotypes lacking human associations. Additionally, EvORanker was made accessible as a user-friendly web tool.

Results

In the analyzed exomic cohort, EvORanker accurately identified the “true” disease gene as the top candidate in 69% of cases and within the top 5 candidates in 95% of cases, consistent with results from the simulated dataset. Notably, EvORanker outperformed existing methods, particularly for poorly annotated genes. In the case of the 6260 knockout genes with mouse phenotypes, EvORanker linked 41% of these genes to observed human disease phenotypes. Furthermore, in two unsolved cases, EvORanker successfully identified DLGAP2 and LPCAT3 as disease candidates for previously uncharacterized genetic syndromes.

Conclusions

We highlight clade-based phylogenetic profiling as a powerful systematic approach for prioritizing potential disease genes. Our study showcases the efficacy of EvORanker in associating poorly annotated genes to disease phenotypes observed in patients. The EvORanker server is freely available at https://ccanavati.shinyapps.io/EvORanker/.
Usefulness of 18F-FDG PET-CT for assessing large-vessel involvement in patients with suspected giant cell arteritis and negative temporal artery biopsy
Authors: Narváez Javier , Estrada Paula , Vidal-Montal Paola , Sánchez-Rodríguez Iván , Sabaté-Llobera Aida , Nolla Joan Miquel , Cortés-Romera Montserrat
Published: January 2024

Objective

To investigate the usefulness of 18F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB).

Methods

A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months.

Results

Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records.

Of the 73 patients finally diagnosed with GCA, 18F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis.

Overall, the diagnostic performance of 18F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA.

Conclusion

Our study confirms the utility of 18F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.
A retrospective analysis of the safety of tacrolimus use and its optimal cut-off concentration during pregnancy in women with systemic lupus erythematosus: study from two Japanese tertiary referral centers
Authors: Nakai Takehiro , Honda Nanase , Soga Eri , Fukui Sho , Kitada Ayako , Yokogawa Naoto , Okada Masato
Published: January 2024

Background

Tacrolimus is one of the major treatment options for systemic lupus erythematosus (SLE) and is considered to be a pregnancy-compatible medication. Since little is known about tacrolimus safety during pregnancy complicated by SLE, this study was designed.

Methods

We included SLE pregnant patients who were followed up at two Japanese tertiary referral centers. We performed multivariate logistic regression analysis to assess each adverse pregnancy outcome (APO) risk. Moreover, we assessed the influence of tacrolimus on the APO ratio in pregnant patients with lupus nephritis, and the impact of combined tacrolimus-aspirin therapy on the APO ratio relative to patients exclusively administered tacrolimus.

Results

Of the 124 pregnancies, 29 were exposed to tacrolimus. Multivariate analysis showed no statistical difference in APO ratio. (overall APO: adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.23–2.03; p = 0.50; maternal APO: aOR, 1.17; 95% CI, 0.36–3.83; p = 0.80; neonatal APO: aOR, 1.10; 95% CI, 0.38–3.21; p = 0.86; PROMISSE APO: aOR, 0.50; 95% CI, 0.14–1.74; p = 0.27).

Blood pressure and estimated glomerular filtration rate (eGFR) during pregnancy and after delivery did not differ between the two groups. Receiver operating characteristic (ROC) curve showed that tacrolimus concentration > 2.6 ng/ml was related to reduced preterm birth rate. (AUC = 0.85, 95% CI: 0.61–1.00, sensitivity: 93% and specificity: 75%).

Regarding effect of tacrolimus on lupus nephritis during pregnancy, tacrolimus showed no increased risk of APO, blood pressure or eGFR during pregnancy and after delivery. (overall APO: OR, 1.00; 95% CI, 0.25–4.08; p = 0.98; maternal APO: OR 1.60, 95% CI, 0.39–6.64; p = 0.51; neonatal APO: OR, 0.71; 95% CI, 0.17–3.03; p = 0.65, PROMISSE APO: OR, 0.50; 95% CI, 0.08–3.22; p = 0.47).

Tacrolimus-aspirin combination therapy showed a protective tendency against hypertensive disorders during pregnancy, preeclampsia and low birth weight.

Conclusions

Tacrolimus use during pregnancy with SLE and lupus nephritis showed no significant influence on APO, blood pressure, or renal function; therefore tacrolimus may be suitable for controlling lupus activity during pregnancy. In addition, when using tacrolimus during pregnancy, we should aim its trough concentration ≥ 2.6 ng/ml while paying careful attention to possible maternal side effects of tacrolimus.

Trial registration

Retrospectively registered.
Acute exposure of microwave impairs attention process by activating microglial inflammation
Authors: Jiang Shaofei , Ma Yingping , Shi Yuan , Zou Yong , Yang Zhenqi , Zhi Weijia , Zhao Zhe , Shen Wei , Chen Liping , Wu Yan , Wang Lifeng , Hu Xiangjun , Wu Haitao
Published: January 2024

Background

Attention provides the foundation for cognitions, which was shown to be affected by microwave (MW) radiation. With the ubiquitous of microwaves, public concerns regarding the impact of MW radiation on attention has hence been increased. Our study aims to investigate the potential effect and mechanism of acute microwave exposure on attention.

Results

We identified obvious impairment of attention in mice by the five-choice serial reaction time (5-CSRT) task. Proteomic analysis of the cerebrospinal fluid (CSF) revealed neuroinflammation and microglial activation potentially due to acute MW exposure. Moreover, biochemical analysis further confirmed microglial activation in the prefrontal cortex (PFC) of mice subjected to acute MW exposure. Finally, minocycline, a commercially available anti-inflammatory compound, attenuated neuroinflammation, inhibited the upregulation of N-methyl-D-aspartic acid receptor (NMDAR) including NR2A and NR2B, and also accelerated the attentional recovery after MW exposure.

Conclusions

We believe that microglial activation and NMDAR upregulation likely contribute to inattention induced by acute MW exposure, and we found that minocycline may be effective in preventing such process.
Threshold effects of technology import on industrial employment: a panel smooth transition regression approach
Authors: Bouattour Afef , Kalai Maha , Helali Kamel
Published: January 2024

The relationship between imported technology and employment is a controversial issue. This study aims to test the hypothesis that the relationship between imported technology and employment is non-linear and evolves with the level of technology imports. The study covers two groups of developed and developing countries over the period 2000–2019. The Panel Smooth Transition Regression (PSTR) model is used to estimate the technology import threshold and its impact on industrial employment. The study finds a positive relationship between imported technology and industrial employment for technology import rates above the 13.667% threshold, above which imported technology begins to improve industrial employment in developed countries. In contrast, for developing countries, the results showed a negative relationship between imported technology and industrial employment for technology import rates above the 3.44% threshold above which imported technology begins to reduce industrial employment. These results suggest that the threshold level of technology imports can be considered as an indicator for promoting innovation policies in both developed and developing countries to minimize the negative effect of process innovation resulting from imported technology.
Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials
Authors: Kataoka Haruki , Nirengi Shinsuke , Matsui Yuka , Taniguchi Hirokazu
Published: January 2024

Background

Human brown adipose tissue (BAT) activity is associated with lower body fatness and favorable glucose metabolism. Previous studies reported that oral fructose loading induces postprandial fibroblast growth factor 21 (FGF21) secretion. FGF21 is a known inducer of adipose tissue thermogenesis; however, the effects of diet-induced FGF21 secretion on BAT thermogenesis remain to be elucidated.

Methods

The effects of both single load and daily consumption of fructose on BAT activity were examined using a randomized cross-over trial and a 2-week randomized controlled trial (RCT), respectively. In the cross-over trial, 15 young men consumed a single dose of fructose solution or water and then consumed the other on a subsequent day. The RCT enrolled 22 young men, and the participants were allocated to a group that consumed fructose and a group that consumed water daily for 2 weeks. BAT activity was analyzed using thermography with cold exposure. Plasma FGF21 level was determined by enzyme-linked immunosorbent assay.

Results

In the cross-over single-load trial, plasma FGF21 levels were significantly increased at 2 h after oral fructose load (p < 0.01); however, there was no significant difference in BAT activity between the fructose load and drinking water. The 2-week RCT revealed that both plasma FGF21 levels and BAT activity were not significantly increased by daily fructose consumption compared to water. Correlation analyses revealed that BAT activity at the baseline and the final measurements were strongly and positively associated with the RCT (r = 0.869, p < 0.001). Changes in BAT activity were significantly and negatively correlated with changes in plasma glucose levels during the 2-week intervention (r = − 0.497, p = 0.022).

Conclusions

Oral fructose load induces a temporary increase in circulating FGF21 levels; however, this does not activate BAT thermogenesis in healthy young men. Further studies are needed to elucidate the effect of endogenous FGF21 on physiological function.

Trial registration

This study is registered with the University Hospital Medical Information Network in Japan (number 000051761, registered 1 August 2023, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052680).
Histogram analysis based on unenhanced CT for identifying thymoma and lymphoma among prevascular mediastinal incidentalomas
Authors: Liu Ming , Zhang Yang , Liu Li-Heng
Published: January 2024

Objective

To determine whether histogram analysis based on unenhanced CT can play a role in the differential diagnosis of thymoma and lymphoma from thymic hyperplasia and cyst (mean CT attenuation > 10 HU).

Materials and methods

This retrospective study included consecutive asymptomatic participants who have prevascular mediastinal lesions incidentally detected by unenhanced CT between December 2013 and August 2020, and with definitive diagnosis by pathology or additional radiologic work-ups. A total of thirteen histogram parameters on enhanced CT were calculated for each lesion, then were compared between tumor (thymoma + lymphoma) and non-tumor (hyperplasia + cyst). Receiver operating characteristic analysis was conducted to investigate the performance of histogram parameter for identifying tumor.

Results

The study population included 192 patients (106 men and 86 women) with a mean age of 50.5 years at the time of CT examination. Of them, 94 patients have tumor (87 thymomas and 7 lymphoma) and 98 have non-tumor (48 thymic hyperplasia and 50 cysts). Nine of the thirteen histogram parameters revealed significant difference between the two groups, including median, minimum, range, 10th percentile, 90th percentile, kurtosis, skewness, uniformity and entropy. No significant difference was observed in the mean CT attenuation between groups. Higher median was found to be independent predictors for distinguishing tumor from non-tumor, and can achieve an area under the curve (AUC) of 0.785 (95% confidence interval [95% IC], 0.720–0.841).

Conclusions

Histogram analysis based on unenhanced CT may be able to provide some help in the differential diagnosis of incidental lesions in prevascular mediastinal.

Grand support

This study was sponsored by Natural Science Foundation of Shanghai (No. 21ZR1459700).
Relationships among return and liquidity of cryptocurrencies
Authors: Zhang Mianmian , Zhu Bing , Li Ziyuan , Jin Siyuan , Xia Yong
Published: January 2024

The cryptocurrency market is a complex and rapidly evolving financial landscape in which understanding the inter- and intra-asset dependencies among key financial variables, such as return and liquidity, is crucial. In this study, we analyze daily return and liquidity data for six major cryptocurrencies, namely Bitcoin, Ethereum, Ripple, Binance Coin, Litecoin, and Dogecoin, spanning the period from June 3, 2020, to November 30, 2022. Liquidity is estimated using three low-frequency proxies: the Amihud ratio and the Abdi and Ranaldo (AR) and Corwin and Schultz (CS) estimators. To account for autoregressive and persistent effects, we apply the autoregressive integrated moving average-generalized autoregressive conditional heteroscedasticity (ARIMA-GARCH) model and subsequently utilize the copula method to examine the interdependent relationships between the return on and liquidity of the six cryptocurrencies. Our analysis reveals strong cross-asset lower-tail dependence in return and significant cross-asset upper-tail dependence in illiquidity measures, with more pronounced dependence observed in specific cryptocurrency pairs, primarily involving Bitcoin, Ethereum, and Litecoin. We also observe that returns tend to be higher when liquidity is lower in the cryptocurrency market. Our findings have significant implications for portfolio diversification, asset allocation, risk management, and trading strategy development for investors and traders, as well as regulatory policy-making for regulators. This study contributes to a deeper understanding of the cryptocurrency marketplace and can help inform investment decision making and regulatory policies in this emerging financial domain.
Flipped classroom with gamified technology and paper-based method for teaching vocabulary
Authors: Pratiwi Damar Isti , Fitriati Sri Wuli , Yuliasri Issy , Waluyo Budi
Published: January 2024

While gamified technology integration in vocabulary instruction within a flipped classroom has yielded beneficial teaching outcomes, specific studies have raised concerns about potential adverse effects linked to this approach. As a result, conducting a comparative analysis between gamified technology and conventional paper-based methods within the flipped classroom framework has become essential. This analysis aims to foster the development of a targeted teaching approach that adeptly addresses the unique needs of students. This study employed a sequential explanatory research design to examine the effectiveness of flipped classroom with gamified technology and paper-based method in teaching vocabulary to students with different proficiency levels. Quantitative data was gathered from a pretest and a posttest, whilst qualitative data was collected through teachers’ guided reflection. Using Academic Word List (300 target words), control groups employed a paper-based, while experimental groups applied gamified technology (Quizlet, Kahoot!, Quizizz, Socrative, and Google Form), which lasted 10 weeks. The participants were 144 non-English major students who took a general English course in the 2nd semester of 2023. Quantitative data analysis ran in SPSS 25 using Paired Sample t-Test and One-way ANOVA. The qualitative data were analyzed using thematic progression. The results showed that gamified technology did not affect students’ learning outcomes, while the paper-based method resulted conversely. It revealed that the paper-based method is more effective than gamified technology for students in general, with low proficiency and high-proficiency level. Further, teachers’ beliefs admitted distinctive issues that gamified technology was more effective for high-proficiency learners, whereas paper-based was more effective for low-proficiency learners. The difference analysis of quantitative and qualitative data sheds light on discussing threats while implementing gamified technology and possible solutions.
Clinical Outcomes, Blood Utilization, and Ethical Considerations for Pediatric Patients in a Bloodless Medicine and Surgery Program
Authors: Lo Brian D. , Pippa Andrew , Sherd Ish’shah , Scott Andrew V. , Thomas Ananda J. , Hendricks Elizabeth A. , Ness Paul M. , Chaturvedi Shruti , Resar Linda M. S. , Frank Steven M.
Published: January 2024

BACKGROUND:

Pediatric patients requesting bloodless care represent a challenging clinical situation, as parents cannot legally refuse lifesaving or optimal interventions for their children. Here, we report clinical outcomes for the largest series of pediatric inpatients requesting bloodless care and also discuss the ethical considerations.

METHODS:

We performed a single-institution retrospective cohort study assessing 196 pediatric inpatients (<18 years of age) who requested bloodless care between June 2012 and June 2016. Patient characteristics, transfusion rates, and clinical outcomes were compared between pediatric patients receiving bloodless care and those receiving standard care (including transfusions if considered necessary by the clinical team) (n = 37,271). Families were informed that all available measures would be undertaken to avoid blood transfusions, although we were legally obligated to transfuse blood if the child’s life was threatened. The primary outcome was composite morbidity or mortality. Secondary outcomes included percentage of patients transfused, individual morbid events, length of stay, total hospital charges, and total costs. Subgroup analyses were performed after stratification into medical and surgical patients.

RESULTS:

Of the 196 pediatric patients that requested bloodless care, 6.1% (n = 12) received an allogeneic blood component, compared to 9.1% (n = 3392) for standard care patients (P = .14). The most common indications for transfusion were perioperative bleeding and anemia of prematurity. None of the transfusions were administered under a court order. Overall, pediatric patients receiving bloodless care exhibited lower rates of composite morbidity compared to patients receiving standard care (2.6% vs 6.2%; P = .035). There were no deaths in the bloodless cohort. Individual morbid events, length of stay, and total hospital charges/costs were not significantly different between the 2 groups. After multivariable analysis, bloodless care was not associated with a significant difference in composite morbidity or mortality (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.12–1.11; P = .077).

CONCLUSIONS:

Pediatric patients receiving bloodless care exhibited similar clinical outcomes compared to patients receiving standard care, although larger studies with adequate power are needed to confirm this finding. There were no mortalities among the pediatric bloodless cohort. Although a subset of our pediatric bloodless patients received an allogeneic transfusion, no patients required a court order. When delivered in a collaborative and patient-centered manner, blood transfusions can be safely limited among pediatric patients.
Nectar cardenolides and floral volatiles mediate a specialized wasp pollination system
Authors: Burger Hannah , Buttala Samantha , Koch Hauke , Ayasse Manfred , Johnson Steven D. , Stevenson Philip C.
Published: January 2024

Specialization in plant pollination systems can arise from traits that function as filters of flower visitors. This may involve chemical traits such as floral volatiles that selectively attract favoured visitors and non-volatile nectar constituents that selectively deter disfavoured visitors through taste or longer-term toxic effects or both. We explored the functions of floral chemical traits in the African milkweed Gomphocarpus physocarpus, which is pollinated almost exclusively by vespid wasps, despite having nectar that is highly accessible to other insects such as honeybees. We demonstrated that the nectar of wasp-pollinated G. physocarpus contains cardenolides that had greater toxic effects on Apis mellifera honeybees than on Vespula germanica wasps, and also reduced feeding rates by honeybees. Behavioural experiments using natural compositions of nectar compounds showed that these interactions are mediated by non-volatile nectar chemistry. We also identified volatile compounds with acetic acid as a main component in the floral scent of G. physocarpus that elicited electrophysiological responses in wasp antennae. Mixtures of these compounds were behaviourally effective for attraction of V. germanica wasps. The results show the importance of both volatile and non-volatile chemical traits as filters that lead to specialization in plant pollination systems.
The processing of proprioceptive signals in distributed networks: insights from insect motor control
Authors: Gebehart Corinna , Büschges Ansgar
Published: January 2024

The integration of sensory information is required to maintain body posture and to generate robust yet flexible locomotion through unpredictable environments. To anticipate required adaptations in limb posture and enable compensation of sudden perturbations, an animal's nervous system assembles external (exteroception) and internal (proprioception) cues. Coherent neuronal representations of the proprioceptive context of the body and the appendages arise from the concerted action of multiple sense organs monitoring body kinetics and kinematics. This multimodal proprioceptive information, together with exteroceptive signals and brain-derived descending motor commands, converges onto premotor networks – i.e. the local neuronal circuitry controlling motor output and movements – within the ventral nerve cord (VNC), the insect equivalent of the vertebrate spinal cord. This Review summarizes existing knowledge and recent advances in understanding how local premotor networks in the VNC use convergent information to generate contextually appropriate activity, focusing on the example of posture control. We compare the role and advantages of distributed sensory processing over dedicated neuronal pathways, and the challenges of multimodal integration in distributed networks. We discuss how the gain of distributed networks may be tuned to enable the behavioral repertoire of these systems, and argue that insect premotor networks might compensate for their limited neuronal population size by, in comparison to vertebrate networks, relying more heavily on the specificity of their connections. At a time in which connectomics and physiological recording techniques enable anatomical and functional circuit dissection at an unprecedented resolution, insect motor systems offer unique opportunities to identify the mechanisms underlying multimodal integration for flexible motor control.
Decifrando a esfinge da burocracia subnacional no federalismo brasileiro: O que se esconde por trás dessa realidade?
Authors: Grin Eduardo , Gonçalves Danilo
Published: January 2024

Este artigo aborda o tema das burocracias subnacionais e a forma como gradualmente ao estudos na literatura nacional vêm ampliado a análise da sua estrutura e funcionamento em estados e municípios. Após uma geração de estudos sobre o poder local mais voltada para analisar democracia e participação, mais recentemente a compreensão das burocracias subnacionais vem assumindo relevância nos marcos da descentralização de atribuições para estados e municípios, o que demanda mais capacidade burocrática. O trabalho também mapeia o debate sobre as burocracias subnacionais na literatura internacional e nacional. Descreve-se a realidade do funcionalismo público estadual e municipal no contexto do federalismo descentralizado comparado com o governo central para evidenciar sua expansão e os efeitos causados na administração pública dessas esferas de governo. Por fim, são sugeridos temas emergentes nesta incipiente agenda de pesquisa para estudos quantitativos e estudos de caso.