bluuebunny/crossref_metadata_2025 huggingface dataset:
The construction of a testis transcriptional cell atlas from embryo to adult reveals various somatic cells and their molecular roles
Authors: Salehi Najmeh , Totonchi Mehdi
Published: November 2023

Background

The testis is a complex organ that undergoes extensive developmental changes from the embryonic stage to adulthood. The development of germ cells, which give rise to spermatozoa, is tightly regulated by the surrounding somatic cells.

Methods

To better understand the dynamics of these changes, we constructed a transcriptional cell atlas of the testis, integrating single-cell RNA sequencing data from over 26,000 cells across five developmental stages: fetal germ cells, infants, childhood, peri-puberty, and adults. We employed various analytical techniques, including clustering, cell type assignments, identification of differentially expressed genes, pseudotime analysis, weighted gene co-expression network analysis, and evaluation of paracrine cell–cell communication, to comprehensively analyze this transcriptional cell atlas of the testis.

Results

Our analysis revealed remarkable heterogeneity in both somatic and germ cell populations, with the highest diversity observed in Sertoli and Myoid somatic cells, as well as in spermatogonia, spermatocyte, and spermatid germ cells. We also identified key somatic cell genes, including RPL39, RPL10, RPL13A, FTH1, RPS2, and RPL18A, which were highly influential in the weighted gene co-expression network of the testis transcriptional cell atlas and have been previously implicated in male infertility. Additionally, our analysis of paracrine cell–cell communication supported specific ligand-receptor interactions involved in neuroactive, cAMP, and estrogen signaling pathways, which support the crucial role of somatic cells in regulating germ cell development.

Conclusions

Overall, our transcriptional atlas provides a comprehensive view of the cell-to-cell heterogeneity in the testis and identifies key somatic cell genes and pathways that play a central role in male fertility across developmental stages.
OTUD1 ameliorates cerebral ischemic injury through inhibiting inflammation by disrupting K63-linked deubiquitination of RIP2
Authors: Zheng Shengnan , Li Yiquan , Song Xiaomeng , Wu Mengting , Yu Lu , Huang Gan , Liu Tengfei , Zhang Lei , Shang Mingmei , Zhu Qingfen , Gao Chengjiang , Chen Lin , Liu Huiqing
Published: November 2023

Background

Inflammatory response triggered by innate immunity plays a pivotal element in the progress of ischemic stroke. Receptor-interacting kinase 2 (RIP2) is implicated in maintaining immunity homeostasis and regulating inflammatory response. However, the underlying mechanism of RIP2 in ischemic stroke is still not well understood. Hence, the study investigated the role and the ubiquitination regulatory mechanism of RIP2 in ischemic stroke.

Methods

Focal cerebral ischemia was introduced by middle cerebral artery occlusion (MCAO) in wild-type (WT) and OTUD1-deficient (OTUD1−/−) mice, oxygen glucose deprivation and reoxygenation (OGD/R) models in BV2 cells and primary cultured astrocytes were performed for monitoring of experimental stroke. GSK2983559 (GSK559), a RIP2 inhibitor was intraventricularly administered 30 min before MCAO. Mice brain tissues were collected for TTC staining and histopathology. Protein expression of RIP2, OTUD1, p-NF-κB–p65 and IκBα was determined by western blot. Localization of RIP2 and OTUD1 was examined by immunofluorescence. The change of IL-1β, IL-6 and TNF-α was detected by ELISA assay and quantitative real-time polymerase chain reaction. Immunoprecipitation and confocal microscopy were used to study the interaction of RIP2 and OTUD1. The activity of NF-κB was examined by dual-luciferase assay.

Results

Our results showed upregulated protein levels of RIP2 and OTUD1 in microglia and astrocytes in mice subjected to focal cerebral ischemia. Inhibition of RIP2 by GSK559 ameliorated the cerebral ischemic outcome by repressing the NF-κB activity and the inflammatory response. Mechanistically, OTUD1 interacted with RIP2 and sequentially removed the K63-linked polyubiquitin chains of RIP2, thereby inhibiting NF-κB activation. Furthermore, OTUD1 deficiency exacerbated cerebral ischemic injury in response to inflammation induced by RIP2 ubiquitination.

Conclusions

These findings suggested that RIP2 mediated cerebral ischemic lesion via stimulating inflammatory response, and OTUD1 ameliorated brain injury after ischemia through inhibiting RIP2-induced NF-κB activation by specifically cleaving K63-linked ubiquitination of RIP2.
Susceptibility of bovine to SARS-CoV-2 variants of concern: insights from ACE2, AXL, and NRP1 receptors
Authors: Ma Ying , Lei Mengyue , Chen Hongli , Huang Pu , Sun Jing , Sun Qiangming , Hu Yunzhang , Shi Jiandong
Published: November 2023

The possibilities of cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans and important livestock species are not yet known. Herein, we used the structural and genetic alignment and surface potential analysis of the amino acid (aa) in angiotensin-converting enzyme 2 (ACE2), tyrosine kinase receptor UFO (AXL), and neuropilin 1 (NRP1) in different species with substantial public health importance. The residues interfacing with the N-terminal domain (NTD) or receptor-binding domain (RBD) of S were aligned to screen the critical aa sites that determined the susceptibility of the SARS-CoV-2 to the host. We found that AXL and NRP1 proteins might be used as the receptors of SARS-CoV-2 in bovines. However, ACE2 protein may not be considered to be involved in the cross-species transmission of SARS-CoV-2 VOCs in cattle because the key residues of the ACE2-S-binding interface were different from those in known susceptible species. This study indicated that emerging SARS-CoV-2 variants potentially expand species tropism to bovines through AXL and NRP1 proteins.
“It has changed my life”: unconditional cash transfers and personalized infant feeding support- a feasibility intervention trial among women living with HIV in western Kenya
Authors: Tuthill Emily L. , Maltby Ann E. , Odhiambo Belinda C. , Hoffmann Thomas J. , Nyaura Maureen , Shikari Rosemary , Cohen Craig R. , Weiser Sheri D.
Published: November 2023

Background

The syndemic effects of poverty, food insecurity and living with HIV are recognized as global health priorities, including through the United Nations Sustainability Goals 1, 2 and 3. Today, women and girls account for 63% of all new HIV infections in eastern and southern Africa, including Kenya. Pregnant and postpartum women living with HIV in this setting face unique challenges including increased financial insecurity as women leave the work force to care for their newborn infants. This contributes to poverty, food scarcity and stress.

Methods

To address financial insecurity, improve infant feeding and reduce stress among mothers living with HIV in this setting, we developed a multilevel intervention, Supporting Healthy Mothers, consisting of 10 monthly unconditional cash transfers (10,000 KES, ~$75 USD/month) and personalized infant feeding support from pregnancy to 7 months postpartum. We conducted a non-randomized feasibility trial of this intervention among women engaged in HIV care in Kisumu, Kenya. From February 23, 2022 to March 23, 2022, we enrolled a total of 40 women who were 20–35 weeks pregnant—20 women to the intervention group at a public clinic, and 20 women to the control group at a similar clinic. Our aim was to assess feasibility, acceptability, and the potential impact of the intervention on food security, infant feeding and maternal mental health.

Results

Analyzing data from all 40 participants, we found a significant reduction in food insecurity scores from baseline for the intervention group when compared to the control group at 6 weeks and 6 months postpartum (p = 0.0008 and p < 0.0001, respectively). Qualitative exit interviews with intervention group participants confirmed women felt more financially secure and had newly acquired practical knowledge and skills related to infant feeding. Women found the two intervention components highly acceptable and described an overall positive impact on wellbeing.

Conclusions

The Supporting Healthy Mothers intervention has potential to positively impact women across the perinatal period and beyond by increasing financial security and supporting women to overcome infant feeding challenges and should be assessed in larger trials.

Trial registration

Supporting Healthy Mothers was registered with ClinicalTrials.gov Protocol Registration and Results System, initially published on February 1, 2022. ClinicalTrials.gov ID: NCT05219552 Protocol ID: K23MH116807.
Results of a cluster randomized trial testing the Systems Analysis and Improvement Approach to increase cervical cancer screening in family planning clinics in Mombasa County, Kenya
Authors: Eastment McKenna C. , Wanje George , Richardson Barbra A. , Mwaringa Emily , Patta Shem , Sherr Kenneth , Barnabas Ruanne V. , Mandaliya Kishorchandra , Jaoko Walter , Mcclelland R. Scott
Published: November 2023

Background

Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya.

Methods

Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics.

Results

In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45–1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74–1.75).

Conclusions

The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA’s implementation with significant disruptions in FP care delivery during the trial. While SAIA’s data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation.

Trial registration

ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.
Successful treatment of cardiogenic shock due to Takotsubo syndrome with implantation of a temporary microaxial left ventricular assist device in transaxillary approach
Authors: von Mackensen Johanna K. R. , Shazly Ahmed El , Schoenrath Felix , Kempfert Joerg , Starck Christoph T. , Potapov Evgenij V. , Jacobs Stephan , Falk Volkmar , Wert Leonhard
Published: November 2023

Objectives

Cardiogenic shock (CS) can occur in patients with Takotsubo syndrome (TTS). As TTS has received increasing attention and has been more closely researched, several aspects of the pathogenesis have been identified, particularly that an excessive release of catecholamines plays an important role. Nevertheless, evidence on specific therapy concepts is still lacking. As a result, TTS with severe hemodynamic instability and low cardiac output creates unique challenges, and mechanical circulatory support is needed with as few inotropic drugs as possible.

Methods

We present a 77-year-old female patient who underwent minimally invasive surgical mitral valve replacement. After an uneventful course, the patient developed acute heart failure eleven days after surgery. Transthoracic echocardiography (TTE) revealed a new onset of TTS. The patient needed left ventricular venting and full haemodynamic flow. We successfully implanted a microaxial left ventricular assist device (Impella 5.5) using the transaxillary approach. The haemodynamic situation stabilised immediately. The patient was weaned and the Impella 5.5 was explanted after five days.

Conclusion

We present the first-in-man implantation of a transaxillary Impella 5.5 in a patient with TTS. The patient benefitted from Impella 5.5 therapy with full haemodynamic support and venting of the left ventricle.
Sternal closure with sandwiched three-piece bioresorbable mesh reduces postoperative hemorrhage: a retrospective study
Authors: Yokoyama Yasutaka , Yamamoto Taira , Oyama Tetsuma , Lee Jiyoung , Machida Yoichiro , Endo Daisuke , Sato Yuichiro , Dohi Shizuyuki , Amano Atsushi , Tabata Minoru
Published: November 2023

Background

Median sternotomy is the most performed procedure in cardiac surgery; however, sternal displacement and bleeding remains a problem. This study aimed to investigate whether sternal reconstruction using a sandwiched three-piece bioresorbable mesh plate can prevent postoperative sternal displacement and bleeding more than a bioresorbable pin.

Methods

Patients (n = 218) who underwent median sternotomy were classified according to whether a sandwiched three-piece bioresorbable mesh plate and wire cerclage (group M, n = 109) or a bioresorbable pin and wire cerclage (group P, n = 109) were used during sternal reconstruction. The causes of postoperative sternal displacement and bleeding with computed tomography data were analyzed and compared between the groups.

Results

The preoperative patient characteristics did not significantly differ between the groups. However, the evaluation of sternal and substernal hematoma on postoperative day 5 using computed tomography showed sternal displacement in 4 (4%) and 22 (20%) patients, and substernal hematoma in 17 (16%) and 41 (38%) patients in groups M and P, respectively; this difference was significant. Furthermore, the amount of bleeding at 6 h postoperatively was lower in group M than in group P (235 ± 147 vs. 284 ± 175 mL, p = 0.0275). Chest reopening, intubation time, and length of intensive care unit and hospital stays did not differ between the groups. The evaluation of substernal hematoma based on computed tomography yielded a significantly lower for group M than for group P, revealing that the mesh plate was an independent predictor of substernal hematoma prevention.

Conclusion

Sternal fixation with a three-piece bioresorbable mesh plate could prevent postoperative sternal displacement, bleeding, and substernal hematoma more than sternal fixation with a pin.
Non-invasive systemic viral delivery of human alpha-synuclein mimics selective and progressive neuropathology of Parkinson’s disease in rodent brains
Authors: Bérard Morgan , Martínez-Drudis Laura , Sheta Razan , El-Agnaf Omar M. A. , Oueslati Abid
Published: November 2023

Background

Alpha-synuclein (α-syn) aggregation into proteinaceous intraneuronal inclusions, called Lewy bodies (LBs), is the neuropathological hallmark of Parkinson’s disease (PD) and related synucleinopathies. However, the exact role of α-syn inclusions in PD pathogenesis remains elusive. This lack of knowledge is mainly due to the absence of optimal α-syn-based animal models that recapitulate the different stages of neurodegeneration.

Methods

Here we describe a novel approach for a systemic delivery of viral particles carrying human α-syn allowing for a large-scale overexpression of this protein in the mouse brain. This approach is based on the use of a new generation of adeno-associated virus (AAV), AAV-PHP.eB, with an increased capacity to cross the blood-brain barrier, thus offering a viable tool for a non-invasive and large-scale gene delivery in the central nervous system.

Results

Using this model, we report that widespread overexpression of human α-syn induced selective degeneration of dopaminergic (DA) neurons, an exacerbated neuroinflammatory response in the substantia nigra and a progressive manifestation of PD-like motor impairments. Interestingly, biochemical analysis revealed the presence of insoluble α-syn oligomers in the midbrain. Together, our data demonstrate that a single non-invasive systemic delivery of viral particles overexpressing α-syn prompted selective and progressive neuropathology resembling the early stages of PD.

Conclusions

Our new in vivo model represents a valuable tool to study the role of α-syn in PD pathogenesis and in the selective vulnerability of nigral DA neurons; and offers the opportunity to test new strategies targeting α-syn toxicity for the development of disease-modifying therapies for PD and related disorders.
Bilayer osteochondral graft in rabbit xenogeneic transplantation model comprising sintered 3D-printed bioceramic and human adipose-derived stem cells laden biohydrogel
Authors: Lee Chih-Yun , Nedunchezian Swathi , Lin Sung-Yen , Su Yu-Feng , Wu Che-Wei , Wu Shun-Cheng , Chen Chung-Hwan , Wang Chih-Kuang
Published: November 2023

Reconstruction of severe osteochondral defects in articular cartilage and subchondral trabecular bone remains a challenging problem. The well-integrated bilayer osteochondral graft design expects to be guided the chondrogenic and osteogenic differentiation for stem cells and provides a promising solution for osteochondral tissue repair in this study. The subchondral bone scaffold approach is based on the developed finer and denser 3D β-tricalcium phosphate (β-TCP) bioceramic scaffold process, which is made using a digital light processing (DLP) technology and the novel photocurable negative thermo-responsive (NTR) bioceramic slurry. Then, the concave-top disc sintered 3D-printed bioceramic incorporates the human adipose-derived stem cells (hADSCs) laden photo-cured hybrid biohydrogel (HG + 0.5AFnSi) comprised of hyaluronic acid methacryloyl (HAMA), gelatin methacryloyl (GelMA), and 0.5% (w/v) acrylate-functionalized nano-silica (AFnSi) crosslinker. The 3D β-TCP bioceramic compartment is used to provide essential mechanical support for cartilage regeneration in the long term and slow biodegradation. However, the apparent density and compressive strength of the 3D β-TCP bioceramics can be obtained for ~ 94.8% theoretical density and 11.38 ± 1.72 MPa, respectively. In addition, the in vivo results demonstrated that the hADSC + HG + 0.5AFnSi/3D β-TCP of the bilayer osteochondral graft showed a much better osteochondral defect repair outcome in a rabbit model. The other word, the subchondral bone scaffold of 3D β-TCP bioceramic could accelerate the bone formation and integration with the adjacent host cancellous tissue at 12 weeks after surgery. And then, a thicker cartilage layer with a smooth surface and uniformly aligned chondrocytes were observed by providing enough steady mechanical support of the 3D β-TCP bioceramic scaffold.
Tolosa-Hunt syndrome and recurrent painful ophthalmoplegic neuropathy, case reports: what to do and when?
Authors: Frattini Daniele , Iodice Alessandro , Spagnoli Carlotta , Rizzi Susanna , Cesaroni Carlo Alberto , Cappella Michela , Fusco Carlo
Published: November 2023

Background

Tolosa-Hunt syndrome (THS) and recurrent painful ophthalmoplegic neuropathy (RPON) are rare diseases reported within the “Painful lesions of the cranial nerves” section of the International Classification of Headache Disorders-3rd edition (ICHD-3). In case of a first painful attack, differential diagnosis could be challenging and many pitfalls are due to the rarity of the disorders and the lack of information about correct medical management in youngsters.

Case presentation

Our main purpose was to report a new case of THS and a new case of RPON describing management and diagnostic investigation at the time of the first episode.

In both cases of THS (13 years old) and RPON (14 years old) a unilateral periorbital headache associated with acute onset of ipsilateral third cranial nerve paresis, scarcely responding to non-steroidal anti-inflammatory drugs (NSAID), was present at the beginning of the first attack. Brain MRI with "time-of-flight" (TOF) angiography and the need to administer steroids (after 72 h from onset) in order to stop pain were the most important handles allowing us to adopt the correct management both in THS or RPON since onset and to face recurrences in RPON by avoiding useless therapy during follow-up.

Conclusion

Unilateral periorbital headache associated with third-fourth or sixth cranial nerve paresis should ideally be investigated with a full work-up, comprehensive of brain MRI with TOF angiography since the first attack. In cases with negative brain MRI spontaneous resolution should be considered and watchful waiting might be advisable before starting steroid therapy.
SCHISTOACT: a protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of praziquantel plus artemisinin-based combinations in the treatment of Schistosoma mansoni infection
Authors: Obonyo Charles O. , Were Vincent O. , Wamae Peter , Muok Erick M. O.
Published: November 2023

Background

Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya.

Methods

The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at − 10 for the risk difference in cure rates between praziquantel and the combined treatment.

Discussion

This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases.

Trial registration

Pan-African Clinical Trials Registry PACTR202001919442161. Retrospectively registered on 6 January 2020
Mosquito (Diptera: Culicidae) populations in contrasting areas of the western regions of Burkina Faso: species diversity, abundance and their implications for pathogen transmission
Authors: Kaboré Didier P. Alexandre , Soma Dieudonné Diloma , Gil Patricia , Kientega Mahamadi , Sawadogo Simon P. , Ouédraogo Georges Anicet , Van de Perre Philippe , Baldet Thierry , Gutierrez Serafin , Dabiré Roch K.
Published: November 2023

Background

Mosquitoes (Diptera: Culicidae) can have a significant negative impact on human health. The urbanization of natural environments and their conversion for agricultural use, as well as human population growth, may affect mosquito populations and increase the risk of emerging or re-emerging mosquito-borne diseases. We report on the variety and number of adult mosquitoes found in four environments with varying degrees of human impact (rural, urban, rice fields, and forest) located in a savannah zone of West Africa.

Methods

Mosquitoes were collected from two regions (Hauts-Bassins and Sud-Ouest) of Burkina Faso during five periods between August 2019 and June 2021. Sampling sites were grouped according to environment. Mosquitoes were collected using BG-Sentinel traps and double net traps, and Prokopack Aspirators. Statistical analyses were performed using R software version 4.1.2. Logistic regression, using generalised mixed linear models, was used to test the effect of environment on mosquito abundance and diversity. Alpha diversity analysis was also performed, using the vegan package.

Results

A total of 10,625 adult mosquitoes were collected, belonging to 33 species and five genera: Culex, Aedes, Anopheles, Mansonia, and Ficalbia. The most dominant species were Culex quinquefasciatus, Anopheles gambiae sensu lato and Aedes aegypti. Alpha diversity was similar in the two regions. Habitat had a significant effect on mosquito species richness, the Shannon index and the Simpson index. The rural environment had the highest species richness (n = 28) followed by the forest environment (n = 24). The highest number of mosquitoes (4977/10,625) was collected in the urban environment.

Conclusions

The species composition of the mosquito populations depended on the type of environment, with fewer species in environments with a high human impact such as urban areas and rice fields. Due to the diversity and abundance of the mosquito vectors, the human populations of all of the environments examined are considered to be at potential risk of mosquito-borne diseases.

Graphical Abstract
A 16-year-old man with leptospirosis and atypical disseminated intravascular coagulation: a case report
Authors: Conreur Charlotte , Coureau Michelle , Grimaldi David , Simonet Olivier , Vallot Frédéric , Ndjekembo Shango Didier
Published: November 2023

Background

Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous–venous extracorporeal membrane oxygenation has been reported in a small number of cases.

Case presentation

We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous–venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous–venous extracorporeal membrane oxygenation, which was discontinued after 12 days.

Conclusion

Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5–7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication.
Trichinella spiralis galectin binding to toll-like receptor 4 induces intestinal inflammation and mediates larval invasion of gut mucosa
Authors: Ma Kai Ning , Zhang Yao , Zhang Zhao Yu , Wang Bo Ning , Song Yan Yan , Han Lu Lu , Zhang Xin Zhuo , Long Shao Rong , Cui Jing , Wang Zhong Quan
Published: November 2023

Previous studies showed that Trichinella spiralis galectin (Tsgal) facilitates larval invasion of intestinal epithelium cells (IECs). However, IEC proteins binding with Tsgal were not identified, and the mechanism by which Tsgal promotes larval invasion is not clear. Toll-like receptors (TLRs) are protein receptors responsible for recognition of pathogens. The aim of this study was to investigate whether recombinant Tsgal (rTsgal) binds to TLR-4, activates inflammatory pathway in gut epithelium and mediates T. spiralis invasion. Indirect immunofluorescence (IIF), GST pull-down and co-immunoprecipitation (Co-IP) assays confirmed specific binding between rTsgal and TLR-4 in Caco-2 cells. qPCR and Western blotting showed that binding of rTsgal with TLR-4 up-regulated the TLR-4 transcription and expression in Caco-2 cells, and activated p-NF-κB p65 and p-ERK1/2. Activation of inflammatory pathway TLR-4/MAPK-NF-κB by rTsgal up-regulated pro-inflammatory cytokines (IL-1β and IL-6) and down-regulated anti-inflammatory cytokine TGF-β in Caco-2 cells, and induced intestinal inflammation. TAK-242 (TLR-4 inhibitor) and PDTC (NF-κB inhibitor) significantly inhibited the activation of TLR-4 and MAPK-NF-κB pathway. Moreover, the two inhibitors also inhibited IL-1β and IL-6 expression, and increased TGF-β expression in Caco-2 cells. In T. spiralis infected mice, the two inhibitors also inhibited the activation of TLR-4/MAPK-NF-κB pathway, ameliorated intestinal inflammation, impeded larval invasion of gut mucosa and reduced intestinal adult burdens. The results showed that rTsgal binding to TLR-4 in gut epithelium activated MAPK-NF-κB signaling pathway, induced the expression of TLR-4 and pro-inflammatory cytokines, and mediated larval invasion. Tsgal might be regarded as a candidate molecular target of vaccine against T. spiralis enteral invasive stage.
Boundary value problems of quaternion-valued differential equations: solvability and Green’s function
Authors: Liu Jie , Sun Siyu , Cheng Zhibo
Published: November 2023

This paper is associated with Sturm–Liouville type boundary value problems and periodic boundary value problems for quaternion-valued differential equations (QDEs). Employing the theory of quaternionic matrices, we prove the conditions for the solvability of the linear boundary valued problem and find Green’s function.
Single VHH-directed BCMA CAR-NK cells for multiple myeloma
Authors: Ren Quan , Zu Yingling , Su Hongchang , Lu Qiumei , Xiang Bin , Luo Yanping , Zhang Jishuai , Song Yongping
Published: November 2023

Natural killer (NK) cells are promising alternatives for the production of “off-the-shelf” CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood (PB) were expanded ex vivo by K562-mbIL21 feeder cells. Stable CAR transduction was obtained through lentiviral transduction with the BaEV-Rless pseudotyped lentiviral vector. BCMA-CD28-IL15 CAR-NK cells with ectopic expression of IL-15 exhibited superior cytotoxicity were compared to BCMA-CD28 CAR-NK cells lacking IL-15 and BCMA-hIgG1-IL15 CAR-NK cells with an IgG1 hinge domain. We further assessed the cytotoxic capabilities of BCMA-2B4-IL15 CAR-NK cells with 2B4 intracellular domain. The BCMA-CD28-IL15 CAR-NK cells revealed stronger cytotoxicity and higher cytokine secretion against BCMA+ tumor cells than BCMA-2B4-IL15 CAR-NK cells in vitro. In the MM.1S-Luc mouse model, BCMA-CD28-IL15 CAR-NK inhibited the growth of tumor cells and prolonged mouse survival. These results show that the single VHH-directed BCMA CAR-NK cells exhibited remarkable specific killing ability, making them a potential candidate for immunotherapy in multiple myeloma treatment.
The effects of zinc supplementation on the metabolic factors in patients with non-alcoholic fatty liver disease: a randomized, double-blinded, placebo-controlled clinical trial
Authors: Rezaei Seyed Mohammad Amin , Mohammadi Farzaneh , Eftekhari Mohammad Hassan , Ejtehadi Fardad , Ghaem Haleh , Mohammadipoor Nazanin
Published: November 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic factors including obesity, dyslipidemia, insulin resistance, oxidative stress, and elevated inflammatory factors. Zinc (Zn) supplementation has been investigated as a potential adjunctive therapy in managing NAFLD outcomes.

Methods

In this randomized, double-blinded, controlled clinical trial, 50 overweight or obese participants with NAFLD were randomized into 2 groups of 25 and received either 30 mg of daily Zn or a placebo for 8 weeks. Both groups were invited to follow a balanced energy-restricted diet and physical activity recommendations.

Results

Based on the between-group comparison, Zn supplementation caused a significant increase in the Zn level (P < 0.001) and a significant decrease in weight (P = 0.004), body mass index (BMI) (P = 0.002), waist circumference (P = 0.010), aspartate transaminase (AST) (P = 0.033), total cholesterol (TC) (P = 0.045), and low-density lipoprotein cholesterol (LDL-C) (P = 0.014), but it had no significant effect on alanine transaminase (ALT), fasting blood sugar (FBS), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein (HDL), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and total antioxidant capacity (TAC) (P > 0.05).

Conclusion

The results of the present study indicated that 8-week supplementation of 30 mg daily Zn may increase the Zn serum level and decline anthropometric parameters, AST, TC, and LDL-C in NAFLD patients, so further research is suggested in the future.

Trial registration

The trial was retrospectively registered at IRCT.ir as IRCT20191015045113N1 (December/8/2019).
Psychometric properties of dyadic data from the Marital Quality Scale of Indonesian Javanese couples
Authors: Nurhayati Siti Rohmah , Setiawati Farida Agus , Amelia Rizki Nor , Fridani Lara
Published: November 2023

Background

Researchers have demonstrated that various measurement concepts and dimensions depend on context and timing.

Objectives

The current study aimed to determine the psychometric properties of the Javanese couples’ marital quality scale based on validity and reliability

Methods

In total 840 participants or 420 marital dyad from Java, Indonesia, were involved in this study. The psychometrics properties scale was analyzed using exploratory and confirmatory factor analysis, convergent and discriminant analysis, and composite reliability.

Results

The exploratory factor analysis found relationship quality to consist of support, physical proximity, warmth, communication, acceptance and respect, role sharing, and responsibility factors. Well-being quality consists of happiness, harmony, and problem-solving. The fit of the measurement model was obtained using confirmatory factor analysis. The fit model was also found in the husband’s and wife’s groups, with no differences between them. The high correlations between wife-husband factors also proved the validity based on convergent and discriminant evidence. The reliability coefficient was high for each dimension and construct.

Discussion

This analysis shows that the marital quality scale developed has information on psychometric properties that can be useful for researchers and the practicians using the marital quality instrument of Javanese couples in particular.
Rift valley fever outbreak in Sembabule District, Uganda, December 2020
Authors: Aceng Freda Loy , Kayiwa Joshua , Elyanu Peter , Ojwang Joseph , Nyakarahuka Luke , Balinandi Stephen , Byakika-Tusiime Jayne , Wejuli Alfred , Harris Julie Rebecca , Opolot John
Published: November 2023

Background

Rift Valley Fever (RVF) is a viral zoonosis that can cause severe haemorrhagic fevers in humans and high mortality rates and abortions in livestock. On 10 December 2020, the Uganda Ministry of Health was notified of the death of a 25-year-old male who tested RVF-positive by reverse-transcription polymerase chain reaction (RT-PCR) at the Uganda Virus Research Institute. We investigated to determine the scope of the outbreak, identify exposure factors, and institute control measures.

Methods

A suspected case was acute-onset fever (or axillary temperature > 37.5 °C) and ≥ 2 of: headache, muscle or joint pain, unexpected bleeding, and any gastroenteritis symptom in a resident of Sembabule District from 1 November to 31 December 2020. A confirmed case was the detection of RVF virus nucleic acid by RT-PCR or serum IgM antibodies detected by enzyme-linked immunosorbent assay (ELISA). A suspected animal case was livestock (cattle, sheep, goats) with any history of abortion. A confirmed animal case was the detection of anti-RVF IgM antibodies by ELISA. We took blood samples from herdsmen who worked with the index case for RVF testing and conducted interviews to understand more about exposures and clinical characteristics. We reviewed medical records and conducted an active community search to identify additional suspects. Blood samples from animals on the index case’s farm and two neighbouring farms were taken for RVF testing.

Results

The index case regularly drank raw cow milk. None of the seven herdsmen who worked with him nor his brother’s wife had symptoms; however, a blood sample from one herdsman was positive for anti-RVF-specific IgM and IgG. Neither the index case nor the additional confirmed case-patient slaughtered or butchered any sick/dead animals nor handled abortus; however, some of the other herdsmen did report high-risk exposures to animal body fluids and drinking raw milk. Among 55 animal samples collected (2 males and 53 females), 29 (53%) were positive for anti-RVF-IgG.

Conclusions

Two human RVF cases occurred in Sembabule District during December 2020, likely caused by close interaction between infected cattle and humans. A district-wide animal serosurvey, animal vaccination, and community education on infection prevention practices campaign could inform RVF exposures and reduce disease burden.
Antenatal diagnosis of thoracopagus and thoraco-omphalopagus conjoined twins: case series
Authors: Charan Bheru Dan , Gangwal Ashish , Jain Savyasachi
Published: November 2023

Background

Conjoined twin pregnancy is a rare variety, which occurs due to incomplete separation of the embryonic plate after 13 days. Each type of this entity is linked to distinct levels of organ sharing, structural abnormalities, complications, and difficulties concerning the potential for separation. So a comprehensive multidisciplinary prenatal assessment of conjoined twins is crucial for providing accurate parental counseling, effectively managing the pregnancy, and formulating an appropriate delivery strategy. The purpose of our study was to early diagnosis of conjoined twins using ultrasound, describing the various types of conjoined twins and the role of recent advances like 3D ultrasound in aiding their management.

Case presentation

Here, we are describing the case series of four conjoined twins, which were diagnosed antenatally by using ultrasound between the period of January 2019 and December 2019. Four cases of conjoined twins (two thoracopagus and two thoraco-omphalopagus) were accurately diagnosed on antenatal ultrasound. After detailed counseling of the parents regarding the risks and benefits of this complicated pregnancy and obtaining written consent, all four cases were terminated. Ultrasound plays a vital role in the early diagnosis and management of conjoined twins. Also, 3D ultrasound and MRI help in better characterization of fused body parts and connection between vital organs, thus it aids in the management.

Conclusions

It is important to detect these cases early as termination of pregnancy is less risky in the early stages as compared to the late stages for proper management.
Does climate risk disclosure shape conservatism? The role of earnings quality in the Egyptian context
Authors: Ismail Tariq H. , Obiedallah Yousra R.
Published: November 2023

The objectives of this study are to (i) examine the relationship between accounting conservatism and climate-related risk disclosure (CRRD) in the context of Egypt, and (ii) look into the moderating role of earnings quality (EQ) in such a relationship. To operationalize CRRD reported by Egyptian firms listed in the SP/EGX ESG index across the years from 2018 to 2022, the study uses a manual content analysis as a base for analysis and employs two (OLS) regression models to test the study’ hypotheses. EQ is measured using the cross-sectional modified Jones model, while accounting conservatism is gauged using the C-Score. Additionally, endogeneity checks in robustness tests are performed using system GMM. The findings show no impact of CRRD on the conservative accounting practices of Egyptian firms. However, there is a sizable adverse effect when EQ is used to moderate this association. This finding is consistent with the notion that firms report high levels of climate impacts and have fewer information asymmetry issues. This paper extends disclosure indexes by highlighting the frequent keywords of CRRD used in the annual narrative reports of Egyptian firms. Hence, this study is among the first to explore the moderation impact of EQ on the relationship between CRRD and accounting conservatism in the Egyptian setting.
Vectorial adaptive optics
Authors: He Chao , Antonello Jacopo , Booth Martin J.
Published: November 2023

Adaptive optics normally concerns the feedback correction of phase aberrations. Such correction has been of benefit in various optical systems, with applications ranging in scale from astronomical telescopes to super-resolution microscopes. Here we extend this powerful tool into the vectorial domain, encompassing higher-dimensional feedback correction of both polarisation and phase. This technique is termed vectorial adaptive optics (V-AO). We show that V-AO can be implemented using sensor feedback, indirectly using sensorless AO, or in hybrid form combining aspects of both. We validate improvements in both vector field state and the focal quality of an optical system, through correction for commonplace vectorial aberration sources, ranging from objective lenses to biological samples. This technique pushes the boundaries of traditional scalar beam shaping by providing feedback control of extra vectorial degrees of freedom. This paves the way for next generation AO functionality by manipulating the complex vectorial field.
Evaluating the Utility and Privacy of Synthetic Breast Cancer Clinical Trial Data Sets
Authors: El Kababji Samer , Mitsakakis Nicholas , Fang Xi , Beltran-Bless Ana-Alicia , Pond Greg , Vandermeer Lisa , Radhakrishnan Dhenuka , Mosquera Lucy , Paterson Alexander , Shepherd Lois , Chen Bingshu , Barlow William E. , Gralow Julie , Savard Marie-France , Clemons Mark , El Emam Khaled
Published: November 2023

PURPOSE

There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques.

METHODS

We synthesized data sets from eight breast cancer clinical trial data sets using three types of generative models: sequential synthesis, conditional generative adversarial network, and variational autoencoder. Synthetic data utility was evaluated by replicating the published analyses on the synthetic data and assessing concordance of effect estimates and CIs between real and synthetic data. Privacy was evaluated by measuring attribution disclosure risk and membership disclosure risk.

RESULTS

Utility was highest using the sequential synthesis method where all results were replicable and the CI overlap most similar or higher for seven of eight data sets. Both types of privacy risks were low across all three types of generative models.

DISCUSSION

Synthetic data using sequential synthesis methods can act as a proxy for real clinical trial data sets, and simultaneously have low privacy risks. This type of generative model can be one way to enable broader sharing of clinical trial data.
Inhibition of Cyclophilin A-Metalloproteinase-9 Pathway Alleviates the Development of Neuropathic Pain by Promoting Repair of the Blood-Spinal Cord Barrier
Authors: Wang Yu , Wang Chenchen , Yang Xuli , Ni Kun , Jiang Li , Xu Li , Liu Qi , Xu Xuan , Gu Xiaoping , Liu Yue , Ma Zhengliang
Published: November 2023

BACKGROUND:

Dysfunction of the blood-spinal cord barrier (BSCB) contributes to the occurrence and development of neuropathic pain (NP). Previous studies revealed that the activation of cyclophilin A (CypA)-metalloproteinase-9 (MMP9) signaling pathway can disrupt the integrity of the blood-brain barrier (BBB) and aggravate neuroinflammatory responses. However, the roles of CypA-MMP9 signaling pathway on BSCB in NP have not been studied. This study aimed to investigate the effect of CypA on the structure and function of the BSCB and pain behaviors in mice with NP.

METHODS:

We first created the mouse chronic constriction injury (CCI) model, and they were then intraperitoneally injected with the CypA inhibitor cyclosporine A (CsA) or vehicle. Pain behaviors, the structure and function of the BSCB, the involvement of the CypA-MMP9 signaling pathway, microglia activation, and expression levels of proinflammatory factors in mice were examined.

RESULTS:

CCI mice presented mechanical allodynia and thermal hyperalgesia, impaired permeability of the BSCB, downregulated tight junction proteins, activated CypA-MMP9 signaling pathway, microglia activation, and upregulated proinflammatory factors, which were significantly alleviated by inhibition of CypA.

CONCLUSIONS:

Collectively, the CypA-MMP9 signaling pathway is responsible for CCI-induced NP in mice by impairing the structure and function of the BSCB, and activating microglia and inflammatory responses.