bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of implementation science theories, models, and frameworks in implementation research for medicinal products: A scoping review
Authors: Smith Meredith Y. , Gaglio Bridget , Anatchkova Milena
Published: January 2024

Background

The uptake, adoption and integration of new medicines and treatment regimens within healthcare delivery can take a decade or more. Increasingly, implementation science (IS) research is being used to bridge this gap between the availability of new therapeutic evidence and its actual application in clinical practice. Little is known, however, about the quality of IS research in this area, including the degree to which theories, models and frameworks (TMFs) are being used. The objective of this study was to conduct a scoping review of the use of TMFs in implementation research involving medicinal products.

Methods

A search was conducted for English language abstracts and manuscripts describing the application of TMFs in IS studies for medicinal products. Eligible publications were those published between 1 January 1974 and 12 December 2022. All records were screened at the title and abstract stage; included full-text papers were abstracted using data extraction tables designed for the study. Study quality was appraised using the Implementation Research Development Tool.

Results

The initial scoping search identified 2697 publications, of which 9 were ultimately eligible for inclusion in the review. Most studies were published after 2020 and varied in their objectives, design and therapeutic area. Most studies had sample sizes of fewer than 50 participants, and all focused on the post-marketing phase of drug development. The TMF most frequently used was the Consolidated Framework for Implementation Research (CFIR). Although most studies applied all TMF domains, TMF use was limited to instrument development and/or qualitative analysis. Quality appraisals indicated the need for engaging patients and other stakeholders in the implementation research, reporting on the cost of implementation strategies, and evaluating the unintended consequences of implementation efforts.

Conclusions

We found that few IS studies involving medicinal products reported using TMFs. Those that did encompassed a wide variety of therapeutic indications and medicinal products; all were in the post-marketing phase and involved limited application of the TMFs. Researchers should consider conducting IS in earlier phases of drug development and integrating the TMFs throughout the research process. More consistent and in-depth use of TMFs may help advance research in this area.
Kawasaki disease in neonates: a case report and literature review
Authors: Shen Mingjun , Liu Die , Ye Fang , Zhang Jing , Wang Jun
Published: January 2024

Background

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that affects infants and young children but is extremely rare in neonates, especially afebrile KD. We present a case of KD without fever in a neonate and review the literature on KD in neonates.

Case presentation

A newborn female was hospitalized because her peripheral blood leukocytes increased for half a day. The admission diagnosis was considered neonatal sepsis and bacterial meningitis. She had no fever since the admission, but a rash appeared on her face by the 7th day. On day 11 after admission, there was a desquamation on the distal extremities. On day 15 after admission, ultrasound showed non-suppurative cervical lymphadenopathy. Echocardiogram revealed coronary artery aneurysms in both sides. Finally, the patient was diagnosed with incomplete KD (IKD). The follow-up echocardiogram showed that the internal diameter of both coronary arteries returned to normal three months after birth.

Conclusions

Fever, rash, and distal extremity desquamation during the recovery phase are the most common symptoms of IKD. When newborns present with clinical manifestations such as rash, distal extremity desquamation and cervical lymph adenitis and with an increased peripheral blood leukocyte count and progressive increase in platelets simultaneously, the medical staff should be highly alert to the possibility of KD even without fever. The echocardiogram needs to be performed promptly. The incidence of coronary artery lesions is significantly higher if neonatal KD patients miss timely diagnosis and treatment.
SRGN amplifies microglia-mediated neuroinflammation and exacerbates ischemic brain injury
Authors: Qian Yi , Yang Lixuan , Chen Jian , Zhou Chao , Zong Ningning , Geng Yang , Xia Shengnan , Yang Haiyan , Bao Xinyu , Chen Yan , Xu Yun
Published: January 2024

Background

Microglia is the major contributor of post-stroke neuroinflammation cascade and the crucial cellular target for the treatment of ischemic stroke. Currently, the endogenous mechanism underlying microglial activation following ischemic stroke remains elusive. Serglycin (SRGN) is a proteoglycan expressed in immune cells. Up to now, the role of SRGN on microglial activation and ischemic stroke is largely unexplored.

Methods

Srgn knockout (KO), Cd44-KO and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO) to mimic ischemic stroke. Exogenous SRGN supplementation was achieved by stereotactic injection of recombinant mouse SRGN (rSRGN). Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological functions were evaluated by the modified neurological severity score (mNSS) and grip strength. Microglial activation was detected by Iba1 immunostaining, morphological analysis and cytokines’ production. Neuronal death was examined by MAP2 immunostaining and FJB staining.

Results

The expression of SRGN and its receptor CD44 was significantly elevated in the ischemic mouse brains, especially in microglia. In addition, lipopolysaccharide (LPS) induced SRGN upregulation in microglia in vitro. rSRGN worsened ischemic brain injury in mice and amplified post-stroke neuroinflammation, while gene knockout of Srgn exerted reverse impacts. rSRGN promoted microglial proinflammatory activation both in vivo and in vitro, whereas Srgn-deficiency alleviated microglia-mediated inflammatory response. Moreover, the genetic deletion of Cd44 partially rescued rSRGN-induced excessed neuroinflammation and ischemic brain injury in mice. Mechanistically, SRGN boosted the activation of NF-κB signal, and increased glycolysis in microglia.

Conclusion

SRGN acts as a novel therapeutic target in microglia-boosted proinflammatory response following ischemic stroke.
What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs?
Authors: Morcel Karine , Merviel Philippe , Bouée Sarah , Le Guillou Mathilde , Carlier Marine , James Pandora , Drapier Hortense , Beauvillard Damien
Published: January 2024

Background

Endometriosis is commonly observed in infertile women and can be staged with regard to severity [e.g. according to the American Fertility Society (AFS) classification]. This condition can cause infertility through impaired oocyte quality, fertilization disorders, tubal lesions, adhesions, deep infiltration, and adenomyosis. Although women with endometriosis often turn to in vitro fertilization (IVF) programs, the literature data on IVF outcomes are sometimes contradictory (i.e. the same as in other etiologies of infertility, or worse). The objective of the present study was to assess and compare pregnancy rates in women with and without endometriosis and according to the endometriosis stage.

Methods

We retrospectively studied clinical and ongoing pregnancy rates in IVF and the cumulative pregnancy rates after frozen/thawed embryo transfers, in women without endometriosis (group A) or with endometriosis (group B). We further compared groups in which endometriosis was staged according to the revised AFS classification: stage 1/2 (group C), stage 3/4 (group D, without endometrioma), and endometrioma alone (group E).

Results

We documented 430 cycles in group A and 460 in group B (including 56 in group C, 88 in group D and 316 in group E). After fresh or frozen/thawed embryo transfers, the differences in ongoing pregnancy rates between groups A and B were not significant. However the cumulative rates per couple were significantly lower (p < 0.05) in group D.

Conclusions

We recommend IVF for women with endometriosis because the pregnancy rates are similar to those observed for women with other types of infertility. This approach is in line with the international guidelines issued by assisted reproductive technology societies. These results again raise the question of whether surgical resection of deep infiltrating endometriosis (stage 3/4) should be recommended before admission to an IVF program.

Trial registration This study was approved by an institutional review board (CPP Ouest VI, Brest, France): reference: B2020CE.43
A method to determine antifungal activity in seed exudates by nephelometry
Authors: Hubert Benjamin , Marchi Muriel , Ly Vu Joseph , Tranchant Camille , Tarkowski Łukasz P. , Leprince Olivier , Buitink Julia
Published: January 2024

Background

One of the levers towards alternative solutions to pesticides is to improve seed defenses against pathogens, but a better understanding is needed on the type and regulation of existing pathways during germination. Dormant seeds are able to defend themselves against microorganisms during cycles of rehydration and dehydration in the soil. During imbibition, seeds leak copious amounts of exudates. Here, we developed a nephelometry method to assay antimicrobial activity (AA) in tomato seed exudates as a proxy to assess level of defenses.

Results

A protocol is described to determine the level of AA against the nonhost filamentous fungus Alternaria brassicicola in the exudates of tomato seeds and seedlings. The fungal and exudate concentrations can be adjusted to modulate the assay sensitivity, thereby providing a large window of AA detection. We established that AA in dormant seeds depends on the genotype. It ranged from very strong AA to complete absence of AA, even after prolonged imbibition. AA depends also on the stages of germination and seedling emergence. Exudates from germinated seeds and seedlings showed very strong AA, while those from dormant seeds exhibited less activity for the same imbibition time. The exudate AA did not impact the growth of a pathogenic fungus host of tomato, Alternaria alternata, illustrating the adaptation of this fungus to its host.

Conclusions

We demonstrate that our nephelometry method is a simple yet powerful bioassay to quantify AA in seed exudates. Different developmental stages from dormant seed to seedlings show different levels of AA in the exudate that vary between genotypes, highlighting a genetic diversity x developmental stage interaction in defense. These findings will be important to identify molecules in the exudates conferring antifungal properties and obtain a better understanding of the regulatory and biosynthetic pathways through the lifecycle of seeds, from dormant seeds until seedling emergence.
Conditions for adherence to videoconference-based programs promoting adapted physical activity in cancer patients: a realist evaluation
Authors: Aromatario Olivier , Cambon Linda , Alla François , Imbert Alexis , Pouchepadass Camille , Renvoisé Nathalie , Dauchy Sarah , Charles Cécile
Published: January 2024

Background

Although moderate physical activity (PA) during cancer treatment has been associated with improved quality of life, reduced side effects, and even lower mortality, many barriers to successful implementation remain. Digital technology has been perceived as an effective lever for overcoming access and motivational issues but few studies have been performed to confirm this assumption. The “VISIO-AJUST” study explored the factors affecting the conditions of adherence to video-conference-based PA programs in patients undergoing cancer treatment.

Methods

The VISIO-AJUST study was based on a qualitative successive case approach, guided by the principles of the realist evaluation, and applied to two French programs of PA, following three main steps: (1) Identification of factors likely to influence conditions of patients’ adherence; (2) Elaboration and testing of explanatory “Context-Mechanism-Outcome (CMO)” configurations; (3) Refinement of CMO configurations, in order to understand what, how, for whom, and under what circumstances video-conference-based PA programs work.

Results

Five main CMO configurations were found to be associated with adherence to video-conferencing-based PA programs, promoting (i) accessibility and a supportive environment for adapted physical activity, (ii) a setting conducive to sociability despite distance, (iii) Confidence and security of practice, (iv) a combination of several motivational levers in favor of continuity of effort and progress, (v) regularity of the sessions, progressiveness in the effort and evaluation of progress as a basis for the adoption of a regular physical practice.

Conclusion

This study provides original insights into the use of videoconferencing to enable patients to improve their PA during cancer treatment. Future research with long-term follow-up would allow for a better understanding of the key conditions promoting sustainable behavior change.
NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport
Authors: Yang Sen , Niou Zhen-Xian , Enriquez Andrea , LaMar Jacob , Huang Jui-Yen , Ling Karen , Jafar-Nejad Paymaan , Gilley Jonathan , Coleman Michael P. , Tennessen Jason M. , Rangaraju Vidhya , Lu Hui-Chen
Published: January 2024

Background

Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer’s, Parkinson’s, and Huntington’s disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose long-projecting axons are often vulnerable in neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring axonal ATP levels for axonal transport, critical for axonal function.

Methods

We generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting a NAD hydrolase, sterile alpha and TIR motif-containing protein 1 (SARM1), prevented axonal deficits caused by NMNAT2 loss. This study used a combination of techniques, including genetics, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos.

Results

We provide in vivo evidence that NMNAT2 in glutamatergic neurons is required for axonal survival. Using in vivo and in vitro studies, we demonstrate that NMNAT2 maintains the NAD-redox potential to provide “on-board” ATP via glycolysis to vesicular cargos in distal axons. Exogenous NAD+ supplementation to NMNAT2 KO neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate both in vitro and in vivo that reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons.

Conclusion

NMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.
Trajectories of post-traumatic stress in sepsis survivors two years after ICU discharge: a secondary analysis of a randomized controlled trial
Authors: Schmidt Konrad F. R. , Gensichen Jochen S. , Schroevers Maya , Kaufmann Martina , Mueller Friederike , Schelling Gustav , Gehrke-Beck Sabine , Boede Monique , Heintze Christoph , Wensing Michel , Schwarzkopf Daniel
Published: January 2024

Background

Post-traumatic stress has been identified as a frequent long-term complication in survivors of critical illnesses after sepsis. Little is known about long-term trajectories of post-traumatic stress and potentially modifiable risk factors following the ICU stay. Study objective was to explore and compare different clinical trajectories of post-traumatic stress symptoms in sepsis survivors up to two years after discharge from ICU.

Methods

Data on post-traumatic stress symptoms by means of the Post-traumatic Symptom Scale (PTSS-10) were collected in sepsis survivors at one, six, 12 and 24 months after discharge from ICU. Data on chronic psychiatric diagnoses prior ICU were derived from the primary care provider’s health records, and data on intensive care treatment from ICU documentation. Trajectories of post-traumatic symptoms were identified ex post, discriminating patterns of change and k-means clustering. Assignment to the trajectories was predicted in multinomial log-linear models.

Results

At 24 months, all follow-up measurements of the PTSS-10 were completed in N = 175 patients. Three clusters could be identified regarding clinical trajectories of PTSS levels: stable low symptoms (N = 104 patients [59%]), increasing symptoms (N = 45 patients [26%]), and recovering from symptoms (N = 26 patients [15%]). Patients with initially high post-traumatic symptoms were more likely to show a decrease (OR with 95% CI: 1.1 [1.05, 1.16]). Females (OR = 2.45 [1.11, 5.41]) and patients reporting early traumatic memories of the ICU (OR = 4.04 [1.63, 10]) were at higher risk for increasing PTSS levels.

Conclusion

Post-traumatic stress is a relevant long-term burden for sepsis patients after ICU stay. Identification of three different trajectories within two years after ICU discharge highlights the importance of long-term observation, as a quarter of patients reports few symptoms at discharge yet an increase in symptoms in the two years following. Regular screening of ICU survivors on post-traumatic stress should be considered even in patients with few symptoms and in particular in females and patients reporting traumatic memories of the ICU.
Geospatial modelling of dry season habitats of the malaria vector, Anopheles funestus, in south-eastern Tanzania
Authors: Kahamba Najat F. , Okumu Fredros O. , Jumanne Mohammed , Kifungo Khamisi , Odero Joel O. , Baldini Francesco , Ferguson Heather M. , Nelli Luca
Published: January 2024

Background

Anopheles funestusis a major malaria vector in Eastern and Southern Africa and is currently the dominant malaria-transmitting vector in many parts of Tanzania. Previous research has identified its preference for specific aquatic habitats, especially those that persist in dry months. This observation suggests the potential for targeted control through precise habitat mapping and characterization. In this study, we investigated the influence of habitat characteristics, land cover and human population densities onAn. funestusdistribution during dry seasons. Based on the results, we developed a habitat suitability model for this vector species in south-eastern Tanzania.

Methods

Eighteen villages in south-eastern Tanzania were surveyed during the dry season from September-December 2021. Water bodies were systematically inspected for mosquito larvae and characterized by their physico-chemical characteristics and surrounding environmental features. A generalized linear model was used to assess the presence ofAn. funestuslarvae as a function of the physico-chemical characteristics, land use and human population densities. The results obtained from this model were used to generate spatially explicit predictions of habitat suitability in the study districts.

Results

Of the 1466 aquatic habitats surveyed, 440 were positive forAn. funestus, with river streams having the highest positivity (74%;n = 322) followed by ground pools (15%;n = 67). The final model had an 83% accuracy in predicting positiveAn. funestushabitats, with the most important characteristics being permanent waters, clear waters with or without vegetation or movement and shading over the habitats. There was also a positive association ofAn. funestuspresence with forested areas and a negative association with built-up areas. Human population densities had no influence onAn. funestusdistribution.

Conclusions

The results of this study underscore the crucial role of both the specific habitat characteristics and key environmental factors, notably land cover, in the distribution ofAn. funestus. In this study area,An. funestuspredominantly inhabits river streams and ground pools, with a preference for clear, perennial waters with shading. The strong positive association with more pristine environments with tree covers and the negative association with built-up areas underscore the importance of ecological transitions in vector distribution and malaria transmission risk. Such spatially explicit predictions could enable more precise interventions, particularly larval source management, to accelerate malaria control.

Graphical Abstract
Covid 19 and diabetes in children: advances and strategies
Authors: Wu Zhaoyuan , Wang Jinling , Ullah Rahim , Chen Minghao , Huang Ke , Dong Guanping , Fu Junfen
Published: January 2024

Background

Throughout the COVID-19 pandemic, there has been a notable increase in the incidence of new-onset diabetes and diabetic ketoacidosis (DKA). Simultaneously, children diagnosed with type 1 diabetes (T1D) have encountered difficulties in maintaining optimal blood glucose levels. The mechanisms underpinning these correlations still remain a puzzle. We reviewed the studies that examined changes in incidence during the pandemic. These studies utilized various metrics for comparison, which encompassed the timing of data collection, diagnostic criteria, as well as the numbers and incidence rates of diabetes and DKA. We found the incidence of diabetes and DKA was higher during the pandemic. As to mechanisms, the invivo and invitro study revealed the factors such as direct viral damage, metabolic dysfunction, and immune responses all attribute to the process of T1D after suffering from COVID-19. Furthermore, we provide some useful strategies to prevent and treat children suffering from diabetes and COVID-19. Conclusions: Strong correlations have been observed between new-onset diabetes and COVID-19. Insights gleaned from clinical descriptions and basic research can offer valuable experience and recommendations for the treatment and prevention of diabetes during future pandemics.
A 6-month exercise intervention clinical trial in women: effects of physical activity on multi-omics biomarkers and health during the first wave of COVID-19 in Korea
Authors: Park JooYong , Kim Jaemyung , Kang Jihyun , Choi Jaesung , Kim Ji-Eun , Min Kyung-Joon , Choi Seong-Woo , Cho Joo-Youn , Lee Miyoung , Choi Ji-Yeob
Published: January 2024

Background

Coronavirus disease 2019 (COVID-19) was first reported in December 2019 and the first case in Korea was confirmed on January 20, 2020. Due to the absence of therapeutic agents and vaccines, the Korean government implemented social distancing on February 29, 2020. This study aimed to examine the effect of physical activity (PA) on health through changes in multi-omics biomarkers with a 6-month of exercise intervention during the first wave of COVID-19 in Korea.

Methods

Twenty-seven healthy middle-aged women were recruited and 14 subjects completed the exercise intervention. The mean age (± SD) was 46.3 (± 5.33) and the mean BMI (± SD) was 24.9 (± 3.88). A total of three blood and stool samples were collected at enrollment, after period 1, and after period 2 (3-month intervals). The amount of PA was measured with an accelerometer and by questionnaire. Clinical variables were used, including blood pressure, grip strength, flexibility, and blood glucose levels and lipid markers obtained from laboratory tests. The concentration of blood metabolites was measured by targeted metabolomics. Fecal microbiome data were obtained by 16 S rRNA gene amplicon sequencing.

Results

During the second half period (period 2), Coronavirus disease 2019 occurred and spread out in Korea, and PA decreased compared with the first half period (period 1) (185.9 ± 168.73 min/week to 102.5 ± 82.30 min/week;p = 0.0101). Blood pressure, hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) decreased in period 1 (p < 0.05) and tended to increase again during period 2 (p < 0.05). Forty metabolites were changed significantly during period 1 (FDRp < 0.05), and we found that 6 of them were correlated with changes in blood pressure, HbA1c, and LDL-C via network analysis.

Conclusions

Our results may suggest that exercise improves health through changes in biomarkers at multi-omics levels. However, reduced PA due to COVID-19 can adversely affect health, emphasizing the necessity for sustained exercise and support for home-based fitness to maintain health.

Trial Registration

The trial is retrospectively registered on ClinicalTrials.gov (NCT05927675; June 30, 2023).
Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration
Authors: Ghoneim Mohamed A. , Gabr Mahmoud M. , El-Halawani Sawsan M. , Refaie Ayman F.
Published: January 2024

Over the past decade, there had been progress in the development of cell therapy for insulin-dependent diabetes. Nevertheless, important hurdles that need to be overcome still remain. Protocols for the differentiation of pluripotent stem cells into pancreatic progenitors or fully differentiated β-cells have been developed. The resulting insulin-producing cells can control chemically induced diabetes in rodents and were the subject of several clinical trials. However, these cells are immunogenic and possibly teratogenic for their transplantation, and an immunoisolation device and/or immunosuppression is needed. A growing number of studies have utilized genetic manipulations to produce immune evasive cells. Evidence must be provided that in addition to the expected benefit, gene manipulations should not lead to any unforeseen complications. Mesenchymal stem/stromal cells (MSCs) can provide a viable alternative. MSCs are widely available from many tissues. They can form insulin-producing cells by directed differentiation. Experimentally, evidence has shown that the transplantation of allogenic insulin-producing cells derived from MSCs is associated with a muted allogeneic response that does not interfere with their functionality. This can be explained by the immunomodulatory functions of the MSC subpopulation that did not differentiate into insulin-producing cells. Recently, exosomes derived from naive MSCs have been used in the experimental domain to treat diabetes in rodents with varying degrees of success. Several mechanisms for their beneficial functions were proposed including a reduction in insulin resistance, the promotion of autophagy, and an increase in the T regulatory population. However, euglycemia was not achieved in any of these experiments. We suggest that exosomes derived from β-cells or insulin-producing cells (educated) can provide a better therapeutic effect than those derived from undifferentiated cells.
Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression
Authors: Lan Xiaofeng , Liu Haiyan , Wang Chengyu , Li Weicheng , Zhang Fan , Hu Zhibo , Chen Xiaoyu , You Zerui , Ning Yuping , Zhou Yanling
Published: January 2024

Background

Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression.

Methods

A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26).

Results

Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009).

Conclusions

Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males.

Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn
Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID)
Authors: Desmedt Luc , Raymond Matthieu , Le Thuaut Aurélie , Asfar Pierre , Darreau Cédric , Reizine Florian , Colin Gwenhaël , Auchabie Johann , Lorber Julien , La Combe Béatrice , Kergoat Pierre , Hourmant Baptiste , Delbove Agathe , Frérou Aurélien , Morin Jean , Ergreteau Pierre Yves , Seguin Philippe , Martin Maëlle , Reignier Jean , Lascarrou Jean-Baptiste , Canet Emmanuel
Published: January 2024

Background

Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients.

Methods

We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes.

Results

The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0–27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00–1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32–3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay.

Conclusion

Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.

Graphical Abstract
Cancer metabolism and carcinogenesis
Authors: Yang Jianqiang , Shay Chloe , Saba Nabil F. , Teng Yong
Published: January 2024

Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing them to adapt to different microenvironments and therapeutic interventions. This refers to metabolic heterogeneity, in which different cell populations use different metabolic pathways to sustain their survival and proliferation and impact their response to conventional cancer therapies. Thus, targeting cancer metabolic heterogeneity represents an innovative therapeutic avenue with the potential to overcome treatment resistance and improve therapeutic outcomes. This review discusses the metabolic patterns of different cancer cell populations and developmental stages, summarizes the molecular mechanisms involved in the intricate interactions within cancer metabolism, and highlights the clinical potential of targeting metabolic vulnerabilities as a promising therapeutic regimen. We aim to unravel the complex of metabolic characteristics and develop personalized treatment approaches to address distinct metabolic traits, ultimately enhancing patient outcomes.
A genomics perspective of personalized prevention and management of obesity
Authors: Gkouskou Kalliopi K. , Grammatikopoulou Maria G. , Lazou Evgenia , Vasilogiannakopoulou Theodora , Sanoudou Despina , Eliopoulos Aristides G.
Published: January 2024

This review discusses the landscape of personalized prevention and management of obesity from a nutrigenetics perspective. Focusing on macronutrient tailoring, we discuss the impact of genetic variation on responses to carbohydrate, lipid, protein, and fiber consumption. Our bioinformatic analysis of genomic variants guiding macronutrient intake revealed enrichment of pathways associated with circadian rhythm, melatonin metabolism, cholesterol and lipoprotein remodeling and PPAR signaling as potential targets of macronutrients for the management of obesity in relevant genetic backgrounds. Notably, our data-based in silico predictions suggest the potential of repurposing the SYK inhibitor fostamatinib for obesity treatment in relevant genetic profiles. In addition to dietary considerations, we address genetic variations guiding lifestyle changes in weight management, including exercise and chrononutrition. Finally, we emphasize the need for a refined understanding and expanded research into the complex genetic landscape underlying obesity and its management.
Avoidant/restrictive food intake disorder differs from anorexia nervosa in delay discounting
Authors: Stern Casey M. , McPherson Iman , Dreier Melissa J. , Coniglio Kathryn , Palmer Lilian P. , Gydus Julia , Graver Haley , Germine Laura T. , Tabri Nassim , Wang Shirley B. , Breithaupt Lauren , Eddy Kamryn T. , Thomas Jennifer J. , Plessow Franziska , Becker Kendra R.
Published: January 2024

Background

Avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) are the two primary restrictive eating disorders; however, they are driven by differing motives for inadequate dietary intake. Despite overlap in restrictive eating behaviors and subsequent malnutrition, it remains unknown if ARFID and AN also share commonalities in their cognitive profiles, with cognitive alterations being a key identifier of AN. Discounting the present value of future outcomes with increasing delay to their expected receipt represents a core cognitive process guiding human decision-making. A hallmark cognitive characteristic of individuals with AN (vs. healthy controls [HC]) is reduced discounting of future outcomes, resulting in reduced impulsivity and higher likelihood of favoring delayed gratification. Whether individuals with ARFID display a similar reduction in delay discounting as those with AN (vs. an opposing bias towards increased delay discounting or no bias) is important in informing transdiagnostic versus disorder-specific cognitive characteristics and optimizing future intervention strategies.

Method

To address this research question, 104 participants (ARFID: n = 57, AN: n = 28, HC: n = 19) completed a computerized Delay Discounting Task. Groups were compared by their delay discounting parameter (ln)k.

Results

Individuals with ARFID displayed a larger delay discounting parameter than those with AN, indicating steeper delay discounting (M ± SD = −6.10 ± 2.00 vs. −7.26 ± 1.73, p = 0.026 [age-adjusted], Hedges’ g = 0.59), with no difference from HC (p = 0.514, Hedges’ g = −0.35).

Conclusion

Our findings provide a first indication of distinct cognitive profiles among the two primary restrictive eating disorders. The present results, together with future research spanning additional cognitive domains and including larger and more diverse samples of individuals with ARFID (vs. AN), will contribute to identifying maintenance mechanisms that are unique to each disorder as well as contribute to the optimization and tailoring of treatment strategies across the spectrum of restrictive eating disorders.
Is the Common Test for University Admissions in Japan enough to measure students’ general English proficiency? The case of the TOEIC Bridge
Authors: Kamiya Nobuhiro
Published: January 2024

This study investigated to what extent the scores of two English tests are correlated to each other, namely, the English test of the Common Test for University Admissions (Common Test, henceforth) in Japan and the TOEIC Bridge, a commercially available English test developed by Educational Testing Service (ETS) that measures four skills of listening, reading, speaking, and writing. Moreover, this study examined to what extent the two tests’ constructs overlap from the viewpoint of L2 competence. In total, 128 university freshmen and high school seniors took the Common Test at the official venues and also the TOEIC Bridge at the researcher’s university (n = 92) or at home (n = 36) a few months later. Results indicated that the scores of the corresponding skills are moderately correlated to each other across the two tests (Reading = .548; Listening = .646; Total = .732). Confirmatory factor analyses demonstrated that the degree of data fitting of the three models of test constructs (unitary, correlated skills, correlated tests) was statistically similar to each other. On the basis of substantive and statistical results, however, we claim that the correlated skills model should be chosen as the best-fit model and, consequently, that the productive skills should be measured in addition to the Common Test.
Formation techniques for upper active channel in monolithic 3D integration: an overview
Authors: Nguyen An Hoang-Thuy , Nguyen Manh-Cuong , Nguyen Anh-Duy , Jeon Seung Joon , Park Noh-Hwal , Lee Jeong-Hwan , Choi Rino
Published: January 2024

The concept of three-dimensional stacking of device layers has attracted significant attention with the increasing difficulty in scaling down devices. Monolithic 3D (M3D) integration provides a notable benefit in achieving a higher connection density between upper and lower device layers than through-via-silicon. Nevertheless, the practical implementation of M3D integration into commercial production faces several technological challenges. Developing an upper active channel layer for device fabrication is the primary challenge in M3D integration. The difficulty arises from the thermal budget limitation for the upper channel process because a high thermal budget process may degrade the device layers below. This paper provides an overview of the potential technologies for forming active channel layers in the upper device layers of M3D integration, particularly for complementary metal-oxide-semiconductor devices and digital circuits. Techniques are for polysilicon, single crystal silicon, and alternative channels, which can solve the temperature issue for the top layer process.
Can training and apprentice programs in STEM increase worker life satisfaction and optimism?
Authors: Chun Yung , Jabbari Jason , Huang Wenrui , Graham Carol
Published: January 2024

Background

Despite the significant relationship between life satisfaction and education, less is known about the connection between life satisfaction and informal learning in the context of training and apprenticeship programs. This paper examines the influence of the LaunchCode program, a novel training and apprentice program in STEM, on participant’s life satisfaction and optimism. We also explore mediating roles of STEM employment and earnings, as well as moderating role of participants’ educational attainment levels.

Results

We find high life satisfaction and optimism among those who completed both the training course and the apprenticeship component. In addition, we find a significant mediation effect of STEM employment on the relationships between program participation and current life satisfaction, as well as optimism, among the apprenticeship completers. Finally, we find a significant moderation effect of one’s education level on the relationship between program completion and finding a STEM job, such that participants with a college degree are more likely to secure STEM employment through coursework alone.

Conclusions

Our findings highlight the significance of apprenticeships in increasing life satisfaction and optimism, as well as the importance of STEM employment in explaining the significant effect of apprenticeships on life satisfaction and optimism. These findings suggest that what people do for a living is more important than how much they earn. However, while apprenticeships may offer an alternative route to the labor market, education may still facilitate connections to STEM employment in the absence of an apprenticeship.
Variation of crater morphological parameters in the landing area of Tianwen-1: relationships with the geological environment and climate change
Authors: Yang Yu , Wang Yi , Li Bo , Ling Zongcheng , Liu Yang , Qu Shaojie , Chen Shengbo
Published: January 2024

The Zhurong rover of the Tianwen-1 mission successfully landed in the southern part of the Utopian Planitia and the northern region of the dichotomy boundary. Craters within a ~ 134 km2 region surrounding the Zhurong rover were identified and divided into seven degradation classes based on their preservation states and morphological details. Assessing how craters have degraded over time provides insight into local surface processes and then speculates on the climate evolution of the study area. The small depth/diameter (d/D) of craters in the study area may be caused by the rapid filling of sediments or by impact processes occurring in poorly cohesive weathering layers, and may also be associated with the volatile material alteration. As time went by, the process of crater degradation is nonlinear, and the degradation rate of the fresh crater in the study area at the initial stage of degradation may be as high as 0.2 m/Myr. The calculated surface erosion rate for the study area is ~ 10–2–10–3 m/Myr, indicating that the erosion of the Martian surface since the Middle Amazonian occurred in the dry environment dominated by wind-sand erosion.

Graphical Abstract
Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study
Authors: Miura Tomotaka , Okuda Tomoki , Suzuki Kodai , Okada Hideshi , Tomita Hiroyuki , Takada Chihiro , Mori Kosuke , Asano Hirotaka , Kano Soichiro , Wakayama Yugo , Fukuda Yohei , Fukuda Hirotsugu , Nishio Ayane , Kawasaki Yuki , Kuroda Ayumi , Suzuki Keiko , Kamidani Ryo , Okamoto Haruka , Fukuta Tetsuya , Kitagawa Yuichiro , Miyake Takahito , Nakane Keita , Suzuki Akio , Yoshida Takahiro , Tetsuka Nobuyuki , Yoshida Shozo , Koie Takuya , Ogura Shinji
Published: January 2024

Background

Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group.

Results

Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment.

Conclusions

Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.
Unsupervised generation of fashion editorials using deep generative model
Authors: Kang Minjoo , Kim Jongsun , Kim Sungmin
Published: January 2024

This research intended to establish a new fashion-related artificial intelligence research topic concerning fashion editorials which could induce streams of further studies. A new fashion editorial dataset, which is a prerequisite in training an AI model, has been established in this study to meet the research purpose. A total of over 150K fashion editorials were initially collected and processed to satisfy necessary dataset conditions. A novel dataset of fashion editorials consisting of approximately 60K editorials is proposed through the process. In order to prove the adequacy of the new dataset, data distribution was analyzed and a generative model was selected and trained to attest that new fashion editorials can be created with the proposed editorial dataset. The results generated by the trained model were qualitatively investigated. The model has shown to have learned various features that compose editorials with the dataset, successfully generating fashion editorials. Quantitative evaluation with FID scores was conducted to support the selection of the generative model used for the qualitative assessment.
Duodenal neuroendocrine tumor after bilateral breast cancer with type 1 neurofibromatosis: a case report
Authors: Fujiwara Sho , Koyamada Nozomi , Miyazawa Koji , Saiki Yuriko , Horii Akira , Miyazaki Shukichi
Published: January 2024

Background

Young women with NF1 are at a high risk of developing breast cancer. Although they are at risk for abdominal tumors, such as gastrointestinal stromal tumors and neuroendocrine tumors, follow-up strategies for other tumors after breast cancer have not yet been established. Here, we present a case of duodenal neuroendocrine tumor found during follow-up after bilateral mastectomy for breast cancer with type 1 neurofibromatosis (NF1), for which pancreaticoduodenectomy (PD) and lymphadenectomy were performed.

Case presentation

A 46-year-old woman with NF1 was referred to our hospital for treatment of a duodenal submucosal tumor. Her previous operative history included bilateral mastectomy for breast cancer: right total mastectomy and left partial mastectomy performed 9 and 5 years ago, respectively. Her daughter was confirmed to have NF1, but her parents were unclear. Although she had no recurrence or symptoms during the follow-up for her breast cancer, she wished to undergo 18-fluorodeoxyglucose–positron emission tomography (FDG–PET) for systemic screening. FDG–PET demonstrated FDG accumulation in the duodenal tumor with a maximum standardized uptake value of 5.78. Endoscopy revealed a 20-mm-diameter tumor in the second duodenal portion, and endoscopic biopsy suggested a NET G1. We performed PD and lymphadenectomy for complete. She was doing well without recurrence and was followed up with PET tomography–computed tomography.

Conclusions

Early detection of gastrointestinal tumors is difficult, because most of them are asymptomatic. Gastrointestinal screening is important for patients with NF1, and PD with lymphadenectomy is feasible for managing duodenal neuroendocrine tumors, depending on their size.