bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of intellectual and developmental disability curriculum in international pre-graduate health professional education
Authors: Vi Lisa , Jiwa Muhammad Irfan , Lunsky Yona , Thakur Anupam
Published: May 2023

Background

Despite the increasing global population of individuals with intellectual and developmental disabilities (IDD), this population remains especially vulnerable to health disparities through several factors such as a lack of access to sufficient medical care and poor determinants of health. To add, numerous studies have shown that healthcare professionals are still insufficiently prepared to support this population of patients. This review synthesizes the literature on current pre-graduate IDD training programs across healthcare professions with the goal of informing the creation of evidence-based curricula.

Methods

Four major databases were searched for current pre-graduate IDD training interventions for healthcare professionals. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis flow diagram and the Best Evidence Medical Educations systematic review guide were used to frame our collection and analysis.

Results

Of the 8601 studies screened, 32 studies were identified, with most studies involving medical students (50%). Of note, 35% of studies were interprofessional. Most interventions utilized multiple pedagogical methods with a majority including clinical experiences (63%) followed by theoretical teaching (59%). Kirkpatrick levels showed 9% were level 0, 6% were level 1, 31% were level 2A, 31% were level 2B, 19% were level 3, 3% were level 4A, and none were level 4B.

Conclusions

There is a paucity of formally evaluated studies in pre-graduate health professional IDD education. As well, there are a lack of longitudinal learning opportunities and integration into formal curriculum. Strengths identified were the use of multimodal approaches to teaching, including interprofessional approaches to optimize team competencies.
A novel step-by-step training program for transanal endoscopic surgery
Authors: Popa Călin , Schlanger Diana , Prunoiu Virgiliu Mihail , Puia Ion Cosmin , Zaharie Florin
Published: May 2023

Background

The objective of our study is to develop an effective training platform for transanal endoscopic surgery and to validate a step-by-step training program for learning the basic skills necessary for this approach.

Methods

We have designed a two-part study: an experimental study (with the aim to design the training platform and the training exercises – on synthetic and biological material) and a prospective analytical study, in order to validate the training program by enrolling as participants general surgery residents and specialists, without previous experience in transanal endoscopic interventions. The performance of the participants was assessed based on the time of completion, as well as the quality of the execution.

Results

We have developed three different diameter platforms (5 cm, 7.5 and 10 cm), that can be used with both the TEO and TAMIS platforms; specific exercises were developed to train different surgical skills like manipulation of tissue, cutting, dissection and suturing. Forty participants were enrolled for the validation of the proposed training program (12 young residents, 16 senior residents and 12 specialist surgeons). A statistically significant improvement of the performance time, from round to round, was observed for all participants in all exercises. The time of completion for the exercises, considering the correct technical execution, was the shortest for more experienced surgeons: specialist surgeons, followed by senior residents and young residents. The biological material exercises, that closely recreate intraoperative conditions and had more strict technical requirements, were difficult to be performed by young residents; better completion rates were seen in senior residents, while all the participants in the specialist surgeons group have completed these exercises.

Conclusions

Our training program is an effective simulation based educational model for recreating intraoperative conditions particular to transanal endoscopic surgery. The proposed step-by-step training program has demonstrated to be useful in developing the important basic skills needed for transanal endoscopic surgery and assured the progress of all the participants, regardless of their surgical experience.
Perspectives of stakeholders regarding the value of maternal and newborn health interventions and practices supported by UNICEF and other partners in the West Nile region of Uganda: a qualitative study
Authors: Muhumuza Simon , Nsabagasani Xavier , Muhangi Cinderella Ngonzi , Latigi Grace , Pirio Patricia , Msukwa Chimwemwe , Mwanyumba Fabian , Gohar Fatima , Hailegebriel Tedbabe Degefie , Asfaw Atnafu Getachew , Bergh Anne-Marie
Published: May 2023

Introduction

Uganda has high maternal, neonatal, and under-five mortality rates. This study documents stakeholder perspectives on best practices in a maternal and newborn health (MNH) quality-improvement programme implemented in the West Nile region of Uganda to improve delivery and utilisation of MNH services.

Methods

This exploratory cross-sectional qualitative study, conducted at the end of 2021, captured the perspectives of stakeholders representing the different levels of the healthcare system. Data were collected in four districts through: interviews with key informants working at all levels of the health system; focus group discussions with parents and caretakers and with community health workers; and interviews with individual community members whose lives had been impacted by the MNH programme. The initial content analysis was followed by a deductive synthesis pitched according to the different levels of the health system and the health-systems building blocks.

Results

The findings are summarised according to the health-systems building blocks and an account is given of three of the interventions most valued by participants: (1) data use for evidence-based decision making (with regard to human resources, essential reproductive health commodities, and financing); (2) establishment of special newborn care units and high-dependency maternity units at district hospitals and training of the health workforce (also with reference to other infrastructural improvements such as the provision of water, sanitation and hygiene facilities at health facilities); and (3) community referral of pregnant women through a commercial motorcycle voucher referral system.

Conclusion

The MNH programme in the West Nile region adopted a holistic and system-wide approach to addressing the key bottlenecks in the planning, delivery, and monitoring of quality MNH services. There was general stakeholder appreciation across the board that the interventions had the potential to improve quality of care and newborn and maternal health outcomes. However, as the funding was largely donor-driven, questions about government ownership and sustainability in the context of limited resources remain.
FGF-trapping hampers cancer stem-like cells in uveal melanoma
Authors: Loda Alessandra , Calza Stefano , Giacomini Arianna , Ravelli Cosetta , Krishna Chandran Adwaid Manu , Tobia Chiara , Tabellini Giovanna , Parolini Silvia , Semeraro Francesco , Ronca Roberto , Rezzola Sara
Published: May 2023

Background

Cancer stem-like cells (CSCs) are a subpopulation of tumor cells responsible for tumor initiation, metastasis, chemoresistance, and relapse. Recently, CSCs have been identified in Uveal Melanoma (UM), which represents the most common primary tumor of the eye. UM is highly resistant to systemic chemotherapy and effective therapies aimed at improving overall survival of patients are eagerly required.

Methods

Herein, taking advantage from a pan Fibroblast Growth Factor (FGF)-trap molecule, we singled out and analyzed a UM-CSC subset with marked stem-like properties. A hierarchical clustering of gene expression data publicly available on The Cancer Genome Atlas (TCGA) was performed to identify patients’ clusters.

Results

By disrupting the FGF/FGF receptor (FGFR)-mediated signaling, we unmasked an FGF-sensitive UM population characterized by increased expression of numerous stemness-related transcription factors, enhanced aldehyde dehydrogenase (ALDH) activity, and tumor-sphere formation capacity. Moreover, FGF inhibition deeply affected UM-CSC survival in vivo in a chorioallantoic membrane (CAM) tumor graft assay, resulting in the reduction of tumor growth. At clinical level, hierarchical clustering of TCGA gene expression data revealed a strong correlation between FGFs/FGFRs and stemness-related genes, allowing the identification of three distinct clusters characterized by different clinical outcomes.

Conclusions

Our findings support the evidence that the FGF/FGFR axis represents a master regulator of cancer stemness in primary UM tumors and point to anti-FGF treatments as a novel therapeutic strategy to hit the CSC component in UM.
Tumor educated platelet: the novel BioSource for cancer detection
Authors: Ding Shanshan , Dong Xiaohan , Song Xingguo
Published: May 2023

Platelets, involved in the whole process of tumorigenesis and development, constantly absorb and enrich tumor-specific substances in the circulation during their life span, thus called “Tumor Educated Platelets” (TEPs). The alterations of platelet mRNA profiles have been identified as tumor markers due to the regulatory mechanism of post-transcriptional splicing. Small nuclear RNAs (SnRNAs), the important spliceosome components in platelets, dominate platelet RNA splicing and regulate the splicing intensity of pre-mRNA. Endogenous variation at the snRNA levels leads to widespread differences in alternative splicing, thereby driving the development and progression of neoplastic diseases. This review systematically expounds the bidirectional tumor-platelets interactions, especially the tumor induced alternative splicing in TEP, and further explores whether molecules related to alternative splicing such as snRNAs can serve as novel biomarkers for cancer diagnostics.
Comparison between a novel helical and a posterior ankle–foot orthosis on gait in people with unilateral foot drop: a randomised crossover trial
Authors: Gasq David , Dumas Raphaël , Caussé Benoit , Scandella Marino , Cintas Pascal , Acket Blandine , Arné-Bes Marie Christine
Published: May 2023

Background

Neuromuscular disease and peripheral neuropathy may cause drop foot with or without evertor weakness. We developed a helical-shaped, non-articulated ankle–foot orthosis (AFO) to provide medial–lateral stability while allowing mobility, to improve gait capacity. Our aim was to evaluate the effect of the helical AFO (hAFO) on functional gait capacity (6-min walk test) in people with peripheral neuropathy or neuromuscular disease (NMD) causing unilateral drop foot and compare with a posterior leaf spring AFO (plsAFO). Secondary aims were to compare functional mobility, 3D kinematic and kinetic gait variables and satisfaction between the AFOs.

Methods

Single centre, randomised crossover trial from January to July 2017 in 20 individuals (14 with peripheral neuropathy and 6 with NMD, 12 females, mean age 55.6 years, SD 15.3); 10 wore the hAFO for the first week and 10 wore the plsAFO before switching for the second week. The 6-min walk test (6MWT), Timed Up and Go (TUG) test and 3D gait analysis were evaluated with the hAFO, the plsAFO and shoes only (noAFO) at inclusion and 1 week after wearing each orthosis. Satisfaction was evaluated with the Quebec user evaluation of satisfaction with assistive technology (QUEST).

Results

Median [interquartile range] 6MWT distance was greater with the hAFO (444 m [79]) than the plsAFO (389 m [135], P < 0.001, Hedge’s g = 0.6) and noAFO (337 m [91], P < 0.001, g = 0.88). TUG time was shorter with the hAFO (8.1 s [2.8]) than the plsAFO (9.5 s [2.6], P < 0.001, g = − 0.5) and noAFO (10.0 s [2.6]), P < 0.001, g = − 0.6). The plsAFO limited plantarflexion during the loading response (plsAFO − 7.5 deg [6.0] vs. noAFO -13.0 deg [10.0], P = 0.0007, g = − 1.0) but the hAFO did not (− 11.0 deg [5.1] vs. noAFO, P = 0.05, g = − 0.5). Quasi-stiffness was lower for the hAFO than plsAFO (P = 0.009, g = − 0.7). The dimensionless eversion moment was higher (though not significantly) with the hAFO than noAFO. Neither orthosis reduced ankle power (P = 0.34). Median total QUEST score was higher for the hAFO (4.7 [0.7]) than the plsAFO (3.6 [0.8]) (P < 0.001, g = 1.9).

Conclusions

The helical orthosis significantly and considerably improved functional gait performance, did not limit ankle mobility, increased lateral stability, though not significantly, and was associated with greater patient satisfaction than the posterior leaf spring orthosis.

Trial registration The trial began before registration was mandatory
Monophasic pericardial synovial sarcoma in a turkish female patient: a very rare case with cyto-histopathological findings
Authors: Yaprak Bayrak Busra , Vural Cigdem , Sezer Huseyin Fatih , Eliçora Aykut , Busra Yaprak
Published: May 2023

Background

The aim was to present a 35-year-old female patient with diagnosis of monophasic primary pericardial synovial sarcoma (PSS) with cytopathological findings.

Case Presentation

The case with back pain, palpitation and weakness, was diagnosed with pericardial effusion and suspicious mass adjacent to right heart in ultrasonography. Computerized tomography showed mass 12 × 11 × 6.5 cm in size, located in right mid-anterior pericardial area, with heterogeneous internal structure, heterogeneously contrasting right heart and prominent pressure on superior vena cava. Cytopathology of pericardial effusion showed monotonous cells with oval-spindle vesicular nuclei, less amphophilic cytoplasm, evenly distributed chromatin and inconspicuous nucleoli. The pericardial mass was resected incompletely, spindle cell mesenchymal tumor with hypercellular fascicular structure and with infiltrative margins, containing a small amount of loose myxoid stroma, occasionally necrotic areas was observed histopathologically. Immunohistochemical positive reaction was for vimentin, Bcl-2, TLE-1. Accordingly, the case was diagnosed with monophasic PSS.

Conclusions

This case of monophasic primary PSS was an extremely rare malignancy diagnosed with the cytopathological findings.
Verification of dried blood spot as a sample type for HIV viral load and early infant diagnosis on Hologic Panther in Zambia
Authors: Simushi Precious , Kalunga Mukoshya Nchima , Mwakyoma Tuku , Mwewa Mulenga , Muchaili Lweendo , Hazeemba Nchimunya , Mulenga Chileshe , Mwewa Patience , Chiyenu Kaseya O. R. , Kachimba John , Choonga Powell , Shibemba Aaron , Hamooya Benison M. , Zambwe Mowa , Chipimo Peter J. , Kasonka Lackson
Published: May 2023

Objective

Zambia has embarked on improving the diagnostic capacity by setting up high throughput and accurate machines in the testing process and introduction of dried blood spot (DBS) as a sample type. This was a cross sectional study to verify dried blood spot as a sample type for HIV viral load and early infant diagnosis (EID) on Hologic Panther platform and Evaluate the analytical performance (precision, linearity and measurement of uncertainty) of the Hologic Panther.

Results

The specificity and sensitivity of EID performance of Aptima Quant Dx assay on Hologic panther machine against the gold standard machine COBAS Taqman (CAP/CTM) was 100% with an overall agreement of 100%. The quantitative HIV Viral Load (VL) accuracy had a positive correlation of (0.96) obtained against the gold standard (plasma samples) run on COBAS4800 platform. Analytical performance of the Hologic panther machine was evaluated; Precision low positive repeatability 3.50154 and within lab 2.268915 at mean 2.88 concentration and precision high positive repeatability 1.116955 and within lab 2.010677 at mean 5.09 concentration were obtained confirming manufacturers claims. Uncertainty of measurement for this study was found to be ± 71 copies/ml. Linearity studies were determined and all points were within acceptable limits. We therefore recommend DBS as a sample type alternative to plasma for the estimation of HIV-1 viral load and EID diagnosis on the Hologic panther machine.
Differential effect of histone H3.3 depletion on retroviral repression in embryonic stem cells
Authors: Tal Ayellet , Aguilera Jose David , Bren Igor , Strauss Carmit , Schlesinger Sharon
Published: May 2023

Background

Integration of retroviruses into the host genome can impair the genomic and epigenomic integrity of the cell. As a defense mechanism, epigenetic modifications on the proviral DNA repress retroviral sequences in mouse embryonic stem cells (ESC). Here, we focus on the histone 3 variant H3.3, which is abundant in active transcription zones, as well as centromeres and heterochromatinized repeat elements, e.g., endogenous retroviruses (ERV).

Results

To understand the involvement of H3.3 in the epigenetic silencing of retroviral sequences in ESC, we depleted the H3.3 genes in ESC and transduced the cells with GFP-labeled MLV pseudovirus. This led to altered retroviral repression and reduced Trim28 recruitment, which consequently led to a loss of heterochromatinization in proviral sequences. Interestingly, we show that H3.3 depletion has a differential effect depending on which of the two genes coding for H3.3, H3f3a or H3f3b, are knocked out. Depletion of H3f3a resulted in a transient upregulation of incoming retroviral expression and ERVs, while the depletion of H3f3b did not have the same effect and repression was maintained. However, the depletion of both genes resulted in a stable activation of the retroviral promoter. These findings suggest that H3.3 is important for regulating retroviral gene expression in mouse ESC and provide evidence for a distinct function of the two H3.3 genes in this regulation. Furthermore, we show that Trim28 is needed for depositing H3.3 in retroviral sequences, suggesting a functional interaction between Trim28 recruitment and H3.3 loading.

Conclusions

Identifying the molecular mechanisms by which H3.3 and Trim28 interact and regulate retroviral gene expression could provide a deeper understanding of the fundamental processes involved in retroviral silencing and the general regulation of gene expression, thus providing new answers to a central question of stem cell biology.
Phenotype and imaging features associated with APP duplications
Authors: Grangeon Lou , Charbonnier Camille , Zarea Aline , Rousseau Stephane , Rovelet-Lecrux Anne , Bendetowicz David , Lemaitre Marion , Malrain Cécile , Quillard-Muraine Muriel , Cassinari Kevin , Maltete David , Pariente Jeremie , Moreaud Olivier , Magnin Eloi , Cretin Benjamin , Mackowiak Marie-Anne , Sillaire Adeline Rollin , Vercelletto Martine , Dionet Elsa , Felician Olivier , Rod-Olivieri Pauline , Thomas-Antérion Catherine , Godeneche Gaelle , Sauvée Mathilde , Cartz-Piver Leslie , Le Ber Isabelle , Chauvire Valérie , Jonveaux Therèse , Balageas Anna-Chloé , Laquerriere Annie , Duyckaerts Charles , Vital Anne , de Paula Andre Maues , Meyronet David , Guyant-Marechal Lucie , Hannequin Didier , Tournier-Lasserve Elisabeth , Campion Dominique ,   CNR-MAJ collaborators, Nicolas Gaël , Wallon David
Published: May 2023

Background

APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers.

Methods

Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls.

Results

Major neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aβ42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia.

Discussion

Phenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA.
Targeting the neural stem cells in subventricular zone for the treatment of glioblastoma: an update from preclinical evidence to clinical interventions
Authors: Li Sijia , Dong Lihua , Pan Zhenyu , Yang Guozi
Published: May 2023

Background

Glioblastoma is one of the most common and aggressive adult brain tumors. The conventional treatment strategy, surgery combined with chemoradiotherapy, did not change the fact that the recurrence rate was high and the survival rate was low. Over the years, accumulating evidence has shown that the subventricular zone has an important role in the recurrence and treatment resistance of glioblastoma. The human adult subventricular zone contains neural stem cells and glioma stem cells that are probably a part of reason for therapy resistance and recurrence of glioblastoma.

Main body

Over the years, both bench and bedside evidences strongly support the view that the presence of neural stem cells and glioma stem cells in the subventricular zone may be the crucial factor of recurrence of glioblastoma after conventional therapy. It emphasizes the necessity to explore new therapy strategies with the aim to target subventricular zone to eradicate neural stem cells or glioma stem cells. In this review, we summarize the recent preclinical and clinical advances in targeting neural stem cells in the subventricular zone for glioblastoma treatment, and clarify the prospects and challenges in clinical application.

Conclusions

Although there remain unresolved issues, current advances provide us with a lot of evidence that targeting the neural stem cells and glioma stem cells in subventricular zone may have the potential to solve the dilemma of glioblastoma recurrence and treatment resistance.
A pumpless monolayer microfluidic device based on mesenchymal stem cell-conditioned medium promotes neonatal mouse in vitro spermatogenesis
Authors: Önen Selin , Atik Ali Can , Gizer Merve , Köse Sevil , Yaman Önder , Külah Haluk , Korkusuz Petek
Published: May 2023

Background

Childhood cancer treatment-induced gonadotoxicity causes permanent infertility/sub-infertility in nearly half of males. The current clinical and experimental approaches are limited to cryopreservation of prepubertal testicular strips and in vitro spermatogenesis which are inadequate to achieve the expanded spermatogonial stem/progenitor cells and spermatogenesis in vitro. Recently, we reported the supportive effect of bone marrow-derived mesenchymal cell co-culture which is inadequate after 14 days of culture in static conditions in prepubertal mouse testis due to lack of microvascular flow and diffusion. Therefore, we generated a novel, pumpless, single polydimethylsiloxane-layered testis-on-chip platform providing a continuous and stabilized microfluidic flow and real-time cellular paracrine contribution of allogeneic bone marrow-derived mesenchymal stem cells.

Methods

We aimed to evaluate the efficacy of this new setup in terms of self-renewal of stem/progenitor cells, spermatogenesis and structural and functional maturation of seminiferous tubules in vitro by measuring the number of undifferentiated and differentiating spermatogonia, spermatocytes, spermatids and tubular growth by histochemical, immunohistochemical, flow cytometric and chromatographic techniques.

Results

Bone marrow-derived mesenchymal stem cell-based testis-on-chip platform supported the maintenance of SALL4(+) and PLZF(+) spermatogonial stem/progenitor cells, for 42 days. The new setup improved in vitro spermatogenesis in terms of c-Kit(+) differentiating spermatogonia, VASA(+) total germ cells, the meiotic cells including spermatocytes and spermatids and testicular maturation by increasing testosterone concentration and improved tubular growth for 42 days in comparison with hanging drop and non-mesenchymal stem cell control.

Conclusions

Future fertility preservation for male pediatric cancer survivors depends on the protection/expansion of spermatogonial stem/progenitor cell pool and induction of in vitro spermatogenesis. Our findings demonstrate that a novel bone marrow-derived mesenchymal stem cell-based microfluidic testis-on-chip device supporting the maintenance of stem cells and spermatogenesis in prepubertal mice in vitro. This new, cell therapy-based microfluidic platform may contribute to a safe, precision-based cell and tissue banking protocols for prepubertal fertility restoration in future.
HSPB7 oppositely regulates human mesenchymal stromal cell-derived osteogenesis and adipogenesis
Authors: Zhang Shuang , van de Peppel Jeroen , Koedam Marijke , van Leeuwen Johannes P. T. M. , van der Eerden Bram C. J.
Published: May 2023

Background

Recent evidence suggests that accumulation of marrow adipose tissue induced by aberrant lineage allocation of bone marrow-derived mesenchymal stromal cells (BMSCs) contributes to the pathophysiologic processes of osteoporosis. Although master regulators of lineage commitment have been well documented, molecular switches between osteogenesis and adipogenesis are largely unknown.

Methods

HSPB7 gene expression during osteogenic and adipogenic differentiation of BMSCs was evaluated by qPCR and Western blot analyses. Lentiviral-mediated knockdown or overexpression of HSPB7 and its deletion constructs were used to assess its function. The organization of cytoskeleton was examined by immunofluorescent staining. ALP activity, calcium assay, Alizarin Red S staining and Oil Red O staining were performed in vitro during osteoblast or adipocyte differentiation. SB431542 and Activin A antibody were used to identify the mechanism of Activin A in the regulation of osteogenic differentiation in BMSCs.

Results

In this study, we identified HSPB7 capable of oppositely regulating osteogenic and adipogenic differentiation of BMSCs. HSPB7 silencing promoted adipogenesis while reducing osteogenic differentiation and mineralization. Conversely, overexpression of HSPB7 strongly enhanced osteogenesis, but no effect was observed on adipogenic differentiation. Deletion of the N-terminal or C-terminal domain of HSPB7 led to decreased osteoblastic potency and mineralization. Mechanistically, our data showed that Activin A is a downstream target participating in HSPB7 knockdown-mediated osteogenic inhibition.

Conclusions

Our findings suggest that HSPB7 plays a positive role in driving osteoblastic differentiation, and with the capability in maintaining the osteo-adipogenesis balance. It holds great promise as a potential therapeutic target in the treatment of bone metabolic diseases.
Racial differences in the major clinical symptom domains of bipolar disorder
Authors: Li Kevin , Richards Erica , Goes Fernando S.
Published: May 2023

Background

Across clinical settings, black individuals are disproportionately less likely to be diagnosed with bipolar disorder compared to schizophrenia, a traditionally more severe and chronic disorder with lower expectations for remission. The causes of this disparity are likely multifactorial, ranging from the effects of implicit bias, to developmental and lifelong effects of structural racism, to differing cultural manifestations of psychiatric symptoms and distress. While prior studies examining differences have found a greater preponderance of specific psychotic symptoms (such as persecutory delusions and hallucinations) and a more dysphoric/mixed mania presentation in Black individuals, these studies have been limited by a lack of systematic phenotypic assessment and small sample sizes. In the current report, we have combined data from two large multi-ethnic studies of bipolar disorder with comparable semi-structured interviews to investigate differences in symptoms presentation across the major clinical symptom domains of bipolar disorder.

Results

In the combined meta-analysis, there were 4423 patients diagnosed with bipolar disorder type I, including 775 of self-reported as Black race. When symptom presentations were compared in Black versus White individuals, differences were found across all the major clinical symptom domains of bipolar disorder. Psychotic symptoms, particularly persecutory hallucinations and both persecutory and mood-incongruent delusions, were more prevalent in Black individuals with bipolar disorder type I (ORs = 1.26 to 2.45). In contrast, Black individuals endorsed fewer prototypical manic symptoms, with a notably decreased likelihood of endorsing abnormally elevated mood (OR = 0.44). Within depression associated symptoms, we found similar rates of mood or cognitive related mood symptoms but higher rates of decreased appetite (OR = 1.32) and weight loss (OR = 1.40), as well as increased endorsement of initial, middle, and early-morning insomnia (ORs = 1.73 to 1.82). Concurrently, we found that black individuals with BP-1 were much less likely to be treated with mood stabilizers, such as lithium (OR = 0.45), carbamazepine (OR = 0.37) and lamotrigine (OR = 0.34), and moderately more likely to be on antipsychotic medications (OR = 1.25).

Conclusions

In two large studies spanning over a decade, we found highly consistent and enduring differences in symptoms across the major clinical symptom domains of bipolar disorder. These differences were marked by a greater burden of mood-incongruent psychotic symptoms, insomnia and irritability, and fewer prototypical symptoms of mania. While such symptoms warrant better recognition to reduce diagnostic disparities, they may also represent potential targets of treatment that can be addressed to mitigate persistent disparities in outcome.
Multi-parametric observations of intermittent hydrothermal water discharge in West Crater of Iwo-Yama volcano, Kirishima Volcanic Complex, Japan
Authors: Tanabe Harutou , Matsushima Takeshi , Aizawa Koki , Muramatsu Dan
Published: May 2023

From April to July 2021, West Crater at Iwo-Yama, Kirishima Volcanic Complex, Japan, was repeatedly filled with hydrothermal water and subsequently evacuated. The overall cycle lasted 14–70 h, and the course of a single cycle followed this sequence of phases: (i) steam effusion disappeared 20–40 min before hydrothermal water discharge; (ii) hydrothermal water discharge occurred, generating a hydrothermal water pool; (iii) steam effusion resumed and gradually increased; and (iv) drain-back (evacuation) of the hydrothermal water occurred 1–1.5 h before the onset of the next hydrothermal water discharge. We used multi-parametric observations (optical camera, thermometer, electric self-potential (SP) electrodes, seismometer, acoustic sensor, and tiltmeter) to investigate the cause of the cyclic hydrothermal water discharge. A change in SP data occurred approximately 2 h before the onset of hydrothermal water discharge. However, the change in SP was small when hydrothermal water discharge did not occur. The temporal change in SP is inferred to have been caused by groundwater flow through the region below West Crater, implying that groundwater flow was occurring 2 h before hydrothermal water discharge. The polarity of SP change suggests that groundwater flowed toward the region underlying the vents. Seismic signals in the frequency range of < 20 Hz decreased 15–45 min after the onset of change in SP. This seismic signal pattern is inferred to have been caused by bubble activity in boiling fluid. We interpret that the inflow of cold groundwater inhibited boiling activity in the conduit, which in turn caused the cessation of both steam effusion and seismic activity. SP data suggest that the inflow of cold groundwater gradually decreased before hydrothermal water discharge. Pressurization sufficient to force the water in the upper part of the conduit to ascend could have built up in the lower part of the conduit owing to a decrease in the input of groundwater into the upper part of the conduit and the continuing supply of steam bubbles and hot water. This increase in pressure finally led to hydrothermal water discharge at the surface. We suggest that the inflow of cold groundwater into the geyser conduit was the key control on the occurrence and cyclicity of hydrothermal water discharge in West Crater at Iwo-Yama.

Graphical Abstract
Eruption style transition during the 2017–2018 eruptive activity at the Shinmoedake volcano, Kirishima, Japan: surface phenomena and eruptive products
Authors: Maeno Fukashi , Shohata Sayaka , Suzuki Yuki , Hokanishi Natsumi , Yasuda Atsushi , Ikenaga Yuya , Kaneko Takayuki , Nakada Setsuya
Published: May 2023

Recent eruptions of the Shinmoedake volcano, Japan, have provided a valuable opportunity to investigate the transition between explosive and effusive eruptions. In October 2017, phreatic/phreatomagmatic explosions occurred. They were followed in March 2018 by a phase of hybrid activity with simultaneous explosions and lava flows and then a transition to intermittent, Vulcanian-style explosions. Evolution of surface phenomena, temporal variations of whole-rock chemical compositions from representative eruptive material samples, and rock microtextural properties, such as the crystallinity and crystal size distribution of juvenile products, are analyzed to characterize the eruption style transition, the conduit location, and the shallow magma conditions of the volcanic edifice. The 2017–2018 eruptive event is also compared with the preceding 2011 explosive–effusive eruption. The chemical and textural properties of the 2018 products (two types of pumice, ballistically ejected lava blocks, and massive lava) are representative of distinct cooling and magma ascent processes. The initial pumice, erupted during lava dome formation, has a groundmass crystallinity of up to 45% and the highest plagioclase number density of all products (1.9 × 106/mm3). Conversely, pumice that erupted later has the lowest plagioclase number density (1.2 × 105/mm3) and the highest nucleation density (23/mm4 in natural logarithm). This 2018 pumice is similar to the 2011 subplinian pumice. Therefore, it was likely produced by undegassed magma with a high discharge rate. Ballistics and massive lava in 2018 are comparable to the 2011 Vulcanian ballistics. Conversely, the high plagioclase number density pumice that occurred in 2018 was not observed during the 2011 eruption. Thus, such pumice might be specific to hybrid eruptions defined by small-scale explosions and lava dome formation with low magma discharge. The observed transitions and temporal variations of the activities and eruption style during the 2017–2018 Shinmoedake eruptions were primarily influenced by the ascent rate of andesitic magma and the geological structure beneath the summit crater.

Graphical Abstract
Risk factors associated with post-weaning diarrhoea in Austrian piglet-producing farms
Authors: René Renzhammer , Sebastian Vetter , Marlies Dolezal , Lukas Schwarz , Annemarie Käsbohrer , Andrea Ladinig
Published: May 2023

Post-weaning diarrhoea (PWD) is a frequent, multifactorial disease of piglets leading to increased mortality rates and high economic losses. Due to the emergence of multi-resistant Escherichia coli isolates and the ban of zinc oxide (ZnO) in the EU since June 2022, alternative measures to prevent PWD are urgently needed. While an abundance of feed supplements is described to prevent PWD, there are hardly any studies reflecting the current situation of PWD in the field. Thus, we aimed to identify differences in management practices, housing and feeding strategies between farms with PWD and farms without PWD. Data were personally collected using a semi-structured questionnaire in 257 Austrian piglet-producing farms. Farms with PWD in more than 10% of all weaned groups within twelve months prior to data collection were defined as case farms (n = 101), while the remaining 136 farms were defined as control farms. Data from 237 farms and 69 explanatory variables were analysed via penalized binary logistic regression using elastic-net in 100 different splits into randomly selected training and test datasets (80:20). Treatment with ZnO and/or colistin (136 farms) was negatively associated with PWD in all splits and had the biggest estimated absolute log odds ratio out of all tested variables. Implementation of an all-in/all-out system in the nursery units and administration of probiotics or horseradish also had preventive effects in most splits (≥ 97%). A higher number of feeding phases for piglets within the first seven weeks of life and housing on fully slatted floors was associated negatively with the occurrence of PWD as well in > 95% of all splits. PWD was more likely to occur on farms having problems with neonatal diarrhoea or postpartum dysgalactia syndrome. While our data demonstrate that treatment with ZnO or colistin had the biggest statistical effect on PWD, we were able to identify other preventive measures like supplementation with probiotics or horseradish. Since implementation of all-in/all-out measures and fully slatted floors were also negatively associated with the occurrence of PWD on visited farms, we assume that reduction of bacterial load by the implementation of simple hygiene measures are still crucial to prevent PWD.
Gut Microbiota Composition and Functionality Are Associated With REM Sleep Duration and Continuous Glucose Levels
Authors: Arnoriaga-Rodríguez María , Leal Yenny , Mayneris-Perxachs Jordi , Pérez-Brocal Vicente , Moya Andrés , Ricart Wifredo , Fernández-Balsells Mercè , Fernández-Real José Manuel
Published: May 2023

Context

Sleep disruption is associated with worse glucose metabolic control and altered gut microbiota in animal models.

Objective

We aimed to evaluate the possible links among rapid eye movement (REM) sleep duration, continuous glucose levels, and gut microbiota composition.

Methods

This observational, prospective, real-life, cross-sectional case-control study included 118 (60 with obesity), middle-aged (39.1-54.8 years) healthy volunteers recruited at a tertiary hospital. Glucose variability and REM sleep duration were assessed by 10-day continuous glucose monitoring (CGM) (Dexcom G6) and wrist actigraphy (Fitbit Charge 3), respectively. The coefficient of variation (CV), interquartile range (IQR), and SD of glucose variability was assessed and the percentage of time in range (% TIR), at 126-139 mg/dL (TIR2), and 140-199 mg/dL (TIR3) were calculated. Shotgun metagenomics sequencing was applied to study gut microbiota taxonomy and functionality.

Results

Increased glycemic variability (SD, CV, and IQR) was observed among subjects with obesity in parallel to increased % TIR2 and % TIR3. REM sleep duration was independently associated with % TIR3 (β = −.339; P < .001) and glucose variability (SD, β = −.350; P < .001). Microbial taxa from the Christensenellaceae family (Firmicutes phylum) were positively associated with REM sleep and negatively with CGM levels, while bacteria from Enterobacteriacea family and bacterial functions involved in iron metabolism showed opposite associations.

Conclusion

Decreased REM sleep duration was independently associated with a worse glucose profile. The associations of species from Christensenellaceae and Enterobacteriaceae families with REM sleep duration and continuous glucose values suggest an integrated picture of metabolic health.
The impact of cell size on morphogen gradient precision
Authors: Adelmann Jan A. , Vetter Roman , Iber Dagmar
Published: May 2023

Tissue patterning during embryonic development is remarkably precise. Here, we numerically determine the impact of the cell diameter, gradient length and the morphogen source on the variability of morphogen gradients. We show that the positional error increases with the gradient length relative to the size of the morphogen source, and with the square root of the cell diameter and the readout position. We provide theoretical explanations for these relationships, and show that they enable high patterning precision over developmental time for readouts that scale with expanding tissue domains, as observed in the Drosophila wing disc. Our analysis suggests that epithelial tissues generally achieve higher patterning precision with small cross-sectional cell areas. An extensive survey of measured apical cell areas shows that they are indeed small in developing tissues that are patterned by morphogen gradients. Enhanced precision may thus have led to the emergence of pseudostratification in epithelia, a phenomenon for which the evolutionary benefit had so far remained elusive.
Απόψεις εκπαιδευτικών πρωτοβάθμιας εκπαίδευσης για τη διαταραχή ελλειματικής προσοχής- υπερκινητικότητας
Authors: Βασιλειάδης Ηλίας , Βλειώρας Γεώργιος , Τσερμεντσελή Στέλλα , Τσακνάκη Αικατερίνη
Published: May 2023

Οι εκτιμήσεις των εκπαιδευτικών για τα παιδιά με ΔΕΠ-Υ καθορίζουν τη μαθησιακή τους πορεία, επηρεάζουν την εικόνα εαυτού που διαμορφώνουν καθώς και τα επίπεδα κοινωνικής αποδοχής από τους συνομήλικους τους. Ωστόσο, ο τρόπος διαχείρισης των συμπτωμάτων της ΔΕΠ-Υ από τους εκπαιδευτικούς στη χώρα μας δεν έχει προσδιοριστεί επαρκώς. Στόχος της παρούσας έρευνας είναι να διερευνηθούν οι πεποιθήσεις των Ελλήνων εκπαιδευτικών πρωτοβάθμιας εκπαίδευσης γενικής αγωγής για τους μαθητές και τις μαθήτριες με ΔΕΠΥ. Οι παράμετροι που συνδέονται με την αντιμετώπιση των δυσκολιών που εμφανίζονται στη τάξη όπου φοιτούν μαθητές με ΔΕΠ-Υ αποτυπώθηκαν με την ηλεκτρονική χορήγηση ερωτηματολόγιου αυτο-αναφοράς, ανοιχτών ερωτήσεων σε 19 εκπαιδευτικούς πρωτοβάθμιας εκπαίδευσης της γενικής αγωγής. Η επεξεργασία των δεδομένων βασίστηκε στις αρχές της διασταυρωμένη ανάλυσης των δεδομένων. Από τα αποτελέσματα της έρευνας προκύπτει ότι η διαχείριση των δυσκολίων των συγκεκριμένων μαθητών δεν μπορεί να είναι αποδοτική με τους παραδοσιακούς παιδαγωγικούς τρόπους. Οι εκπαιδευτικοί, ακολουθώντας το ατομικό-ιατρικό μοντέλο διαχείρισης των συμπεριφορικών δυσκολιών, κρίνουν σημαντική την εξατομικευμένη ψυχο-εκπαιδευτική υποστήριξη των παιδιών με ΔΕΠ-Υ, όχι από τους ίδιους τους εκπαιδευτικούς αλλά από εξειδικευμένο εκπαιδευτικό προσωπικό. Συμπερασματικά, προκρίνεται ο επαναπροσδιορισμός του διακριτού ρόλου των εκπαιδευτικών γενικής αγωγής της πρωτοβάθμιας εκπαίδευσης αναφορικά με τη διαχείριση των μαθητών με ΔΕΠ-Υ εντός της σχολικής τάξης.
THE ROLE OF INSTITUTIONAL FACTORS IN THE DEVELOPMENT OF SMALL BUSINESS IN THE DIGITAL ECONOMY
Authors: Kuzmina Larisa A.
Published: May 2023

The purpose of the article is to theoretically substantiate the influence of institutional factors and, above all, the institutional environment on the development of small business in the conditions of digitalization of the economy. The quality of the institutional environment largely determines the possibilities of unlocking its potential Today, it can be clearly stated that the Russian institutional environment is very unstable due to the crisis situation caused by the tightening of sanctions. Small business has not yet recovered from the pandemic, and the increasing uncertainty in the Russian economy cannot but affect the expectations of small businesses. Small business incomes do not only lack growth, they are shrinking. All this confirms the need to adjust the institutions and mechanisms of the system of state support for small business, taking into account its capabilities in the digital economy. Small businesses objectively feel the need to use digital technologies in their activities, because they allow you to expand its capabilities. This further actualizes the need for systemic measures to support it in various fields of activity in the context of digital transformation.

In the study of the tasks set, the methods of theoretical analysis were used: the method of scientific abstraction, statistical analysis, the method of expert assessments, as well as synthesis, deduction and induction.
METHODS FOR CONCLUDING CONTRACTS IN COMMERCE: THEORETICAL AND PRACTICAL EXPERIENCE OF CONCEPTUALIZATION
Authors: Bolshakova Valentina M. , Amosov Artur A. , Naumov Petr Y.
Published: May 2023

Relevance. An attribute of civilization and the development of legality in society is the proclamation of norms that the right to free use and disposal of one’s abilities and property for entrepreneurial and other economic activities is granted to each subject. At the same time, one of the constitutionally significant values of commercial law is that any obstacles to the free movement of goods, services and finances on the territory of Russia are not allowed.

Purpose, materials and methods. Free trade is a basic principle and human right in a democratic society and the rule of law. This principle provides the possibility of developing foreign and domestic trade, and as a result, the development of the country’s economy, increasing the prestige and influence of the state in the international arena. Restrictions on the freedom of movement of goods may be introduced, but only in exceptional cases and only in accordance with federal law, if it is necessary for the security of the country, the protection and protection of life, human health and cultural values. From the foregoing, it follows that today there are various forms and ways of doing business and trade in Russia. At present, the role of commercial law and its development in the life of society and the state is increasing. Trade turnover ensures the freedom of choice of goods on the market and their availability for everyone. In this regard, the correct drafting and conclusion of contracts in trade is of great importance. However, at the present stage, the issues of an integrated approach to studying the specifics of concluding contracts in trade turnover, due to the complexity of the formation of a doctrinal approach to this topic, remain not fully developed. This is also dictated by the fact that the concept of «contract in trade» is quite new for Russian law. Such agreements are randomly located in various legislative acts, and sometimes their actual appearance is ahead of the legislator, in addition, law enforcement practice in this area is not formed at a sufficient level.

Research results. The article presents the main scientific results of the generalization of ideas about the methods of concluding contracts in trade in circulation. Their essence and modern meaning are also revealed. Current recommendations for improving legislation in this area are also presented. Key words: trade turnover, contract, method of concluding a contract, contract in trade turnover, commercial contract, seller, supplier, buyer, offer, acceptance.