bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-design and mixed methods evaluation of an interdisciplinary digital resource for undergraduate health profession students to improve the prevention, recognition, and management of delirium in Ireland: a study protocol
Authors: Cook Lana , Coffey Alice , Brown Wilson Christine , Boland Pauline , Stark Patrick , Graham Margaret , McMahon James , Tuohy Dympna , Barry Heather E , Murphy Jill , Birch Matt , Tierney Audrey , Anderson Tara , McCurtin Arlene , Cunningham Emma , Curran Geoffrey M. , Mitchell Gary
Published: April 2024

Background

Delirium is a common symptom of acute illness which is potentially avoidable with early recognition and intervention. Despite being a growing concern globally, delirium remains underdiagnosed and poorly reported, with limited understanding of effective delirium education for undergraduate health profession students. Digital resources could be an effective approach to improving professional knowledge of delirium, but studies utilising these with more than one profession are limited, and no evidence-based, interdisciplinary, digital delirium education resources are reported. This study aims to co-design and evaluate a digital resource for undergraduate health profession students across the island of Ireland to improve their ability to prevent, recognise, and manage delirium alongside interdisciplinary colleagues.

Methods

Utilising a logic model, three workstreams have been identified. Workstream 1 will comprise three phases: (1) a systematic review identifying the format, methods, and content of existing digital delirium education interventions for health profession students, and their effect on knowledge, self-efficacy, and behavioural change; (2) focus groups with health profession students to determine awareness and experiences of delirium care; and (3) a Delphi survey informed by findings from the systematic review, focus groups, and input from the research team and expert reference group to identify resource priorities. Workstream 2 will involve the co-design of the digital resource through workshops (n = 4) with key stakeholders, including health profession students, professionals, and individuals with lived experience of delirium. Lastly, Workstream 3 will involve a mixed methods evaluation of the digital resource. Outcomes include changes to delirium knowledge and self-efficacy towards delirium care, and health profession students experience of using the resource.

Discussion

Given the dearth of interdisciplinary educational resources on delirium for health profession students, a co-designed, interprofessional, digital education resource will be well-positioned to shape undergraduate delirium education. This research may enhance delirium education and the self-efficacy of future health professionals in providing delirium care, thereby improving practice and patients’ experiences and outcomes.

Trial registration

Not applicable.
Developing a platform for secretion of biomolecules in Mycoplasma feriruminatoris
Authors: Gonzalez-de-Miguel Javier , Montero-Blay Ariadna , Ciampi Ludovica , Rodriguez-Arce Irene , Serrano Luis
Published: April 2024

Background

Having a simple and fast dividing organism capable of producing and exposing at its surface or secreting functional complex biomolecules with disulphide bridges is of great interest. The mycoplasma bacterial genus offers a set of relevant properties that make it an interesting chassis for such purposes, the main one being the absence of a cell wall. However, due to their slow growth, they have rarely been considered as a potential platform in this respect. This notion may be challenged with the recent discovery of Mycoplasma feriruminatoris, a species with a dividing time close to that of common microbial workhorses. So far, no tools for heterologous protein expression nor secretion have been described for it.

Results

The work presented here develops the fast-dividing M. feriruminatoris as a tool for secreting functional biomolecules of therapeutic interest that could be used for screening functional mutants as well as potentially for protein-protein interactions. Based on RNAseq, quantitative proteomics and promoter sequence comparison we have rationally designed optimal promoter sequences. Then, using in silico analysis, we have identified putative secretion signals that we validated using a luminescent reporter. The potential of the resulting secretion cassette has been shown with set of active clinically relevant proteins (interleukins and nanobodies).

Conclusions

We have engineered Mycoplasma feriruminatoris for producing and secreting functional proteins of medical interest.
Field evaluation of the residual efficacy of new generation insecticides for potential use in indoor residual spray programmes in South Africa
Authors: Maharaj Rajendra , Seocharan Ishen , Lakan Vishan , Nyawo Zuziwe , Mkhabela Moses , Balakrishna Yusentha
Published: April 2024

Background

The decreasing residual efficacy of insecticides is an important factor when making decisions on insecticide choice for national malaria control programmes. The major challenge to using chemicals for vector control is the selection for the development of insecticide resistance. Since insecticide resistance has been recorded for most of the existing insecticides used for indoor residual spraying, namely, DDT, pyrethroids, organophosphates and carbamates, and new chemicals are necessary for the continued success of indoor residual spraying. The aim of this study was to assess the residual efficacy of Actellic 300CS, SumiShield™ 50WG and Fludora®Fusion by spraying on different wall surfaces.

Methods

One hundred and sixty-eight houses with different wall surface types (mud, cement, painted cement, and tin) which represented the rural house wall surface types in KwaZulu-Natal, South Africa were used to evaluate the residual efficacy of Actellic 300CS, SumiShield 50WG and Fludora®Fusion with DDT as the positive control. All houses were sprayed by experienced spray operators from the Malaria Control Programme. Efficacy of these insecticides were evaluated by contact bioassays against Anopheles arabiensis, a vector species. The residual efficacy of the insecticide formulations was evaluated against a susceptible insectary-reared population of An. arabiensis using WHO cone bioassays.

Results

Effectiveness of the three insecticides was observed up to 12 months post-spray. When assessing the achievement of 100% mortality over time, SumiShield performed significantly better than DDT on mud (OR 2.28, 95% CI 1.72–3.04) and painted cement wall types (OR 3.52, 95% CI 2.36–5.26). On cement wall types, Actellic was found to be less effective than DDT (OR 0.55, 95% CI 0.37–0.82) while Fludora®Fusion was less effective on tin wall types (OR 0.67, 95% CI 0.47–0.95). When compared to the combined efficacy of DDT on mud surfaces, SumiShield applied to each of the mud, cement and painted cement wall types and DDT applied to the cement wall types was found to be significantly more effective. These insecticides usually resulted in 100% mortality for up to 12 months with a delayed mortality period of 96–144 h, depending on the insecticide evaluated and the surface type sprayed.

Conclusion

Field evaluation of these insecticides have shown that Actellic, SumiShield and Fludora®Fusion are suitable replacements for DDT. Each of these insecticides can be used for malaria vector control, requiring just one spray round. These insecticides can be used in rotation or as mosaic spraying.
Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex
Authors: Ghonim Mohamed A. , Ju Jihang , Pyakurel Kusma , Ibba Salome V. , Abouzeid Mai M. , Rady Hamada F. , Matsuyama Shigemi , Del Valle Luis , Boulares A. Hamid
Published: April 2024

Background

The DNA-dependent protein kinase (DNA-PK) complex comprises a catalytic (PRKDC) and two requisite DNA-binding (Ku70/Ku80) subunits. The role of the complex in repairing double-stranded DNA breaks (DSBs) is established, but its role in inflammation, as a complex or individual subunits, remains elusive. While only ~ 1% of PRKDC is necessary for DNA repair, we reported that partial inhibition blocks asthma in mice without causing SCID.

Methods

We investigated the central role of PRKDC in inflammation and its potential association with DNA repair. We also elucidated the relationship between inflammatory cytokines (e.g., TNF-α) and PRKDC by analyzing its connections to inflammatory kinases. Human cell lines, primary human endothelial cells, and mouse fibroblasts were used to conduct the in vitro studies. For animal studies, LPS- and oxazolone-induced mouse models of acute lung injury (ALI) and delayed-type hypersensitivity (DHT) were used. Wild-type, PRKDC+/−, or Ku70+/−mice used in this study.

Results

A ~ 50% reduction in PRKDC markedly blocked TNF-α-induced expression of inflammatory factors (e.g., ICAM-1/VCAM-1). PRKDC regulates Th1-mediated inflammation, such as DHT and ALI, and its role is highly sensitive to inhibition achieved by gene heterozygosity or pharmacologically. In endothelial or epithelial cells, TNF-α promoted rapid PRKDC phosphorylation in a fashion resembling that induced by, but independent of, DSBs. Ku70 heterozygosity exerted little to no effect on ALI in mice, and whatever effect it had was associated with a specific increase in MCP-1 in the lungs and systemically. While Ku70 knockout blocked VP-16-induced PRKDC phosphorylation, it did not prevent TNF-α − induced phosphorylation of the kinase, suggesting Ku70 dispensability. Immunoprecipitation studies revealed that PRKDC transiently interacts with p38MAPK. Inhibition of p38MAPK blocked TNF-α-induced PRKDC phosphorylation. Direct phosphorylation of PRKDC by p38MAPK was demonstrated using a cell-free system.

Conclusions

This study presents compelling evidence that PRKDC functions independently of the DNA-PK complex, emphasizing its central role in Th1-mediated inflammation. The distinct functionality of PRKDC as an individual enzyme, its remarkable sensitivity to inhibition, and its phosphorylation by p38MAPK offer promising therapeutic opportunities to mitigate inflammation while sparing DNA repair processes. These findings expand our understanding of PRKDC biology and open new avenues for targeted anti-inflammatory interventions.
Prioritization of maternal and newborn health policies and their implementation in the eastern conflict affected areas of the Democratic Republic of Congo: a political economy analysis
Authors: Bigirinama Rosine Nshobole , Mothupi Mamothena Carol , Mwene-Batu Pacifique Lyabayungu , Kozuki Naoko , Chiribagula Christian Zalinga , Chimanuka Christine Murhim’alika , Ngaboyeka Gaylord Amani , Bisimwa Ghislain Balaluka
Published: April 2024

Background

Maternal and neonatal mortality remains a major concern in the Democratic Republic of Congo (DRC), and the country’s protracted crisis context exacerbates the problem. This political economy analysis examines the maternal and newborn health (MNH) prioritization in the DRC, focussing specifically on the conflict-affected regions of North and South Kivu. The aim is to understand the factors that facilitate or hinder the prioritization of MNH policy development and implementation by the Congolese government and other key actors at national level and in the provinces of North and South Kivu.

Methods

Using a health policy triangle framework, data collection consisted of in-depth interviews with key actors at different levels of the health system, combined with a desk review. Qualitative data were analysed using inductive and then deductive approaches, exploring the content, process, actor dynamics, contextual factors and gender-related factors influencing MNH policy development and implementation.

Results

The study highlighted the challenges of prioritizing policies in the face of competing health and security emergencies, limited resources and governance issues. The universal health coverage policy seems to offer hope for improving access to MNH services. Results also revealed the importance of international partnerships and global financial mechanisms in the development of MNH strategies. They reveal huge gender disparities in the MNH sector at all levels, and the need to consider cultural factors that can positively or negatively impact the success of MNH policies in crisis zones.

Conclusions

MNH is a high priority in DRC, yet implementation faces hurdles due to financial constraints, political influences, conflicts and gender disparities. Addressing these challenges requires tailored community-based strategies, political engagement, support for health personnel and empowerment of women in crisis areas for better MNH outcomes.
Rapid cost-effectiveness analysis: hemodialysis versus peritoneal dialysis for patients with acute kidney injury in Rwanda
Authors: Nemzoff Cassandra , Ahmed Nurilign , Olufiranye Tolulope , Igiraneza Grace , Kalisa Ina , Chadha Sukrit , Hakiba Solange , Rulisa Alexis , Riro Matiko , Chalkidou Kalipso , Ruiz Francis
Published: April 2024

Background

To ensure the long-term sustainability of its Community-Based Health Insurance scheme, the Government of Rwanda is working on using Health Technology Assessment (HTA) to prioritize its resources for health. The objectives of the study were to rapidly assess (1) the cost-effectiveness and (2) the budget impact of providing PD versus HD for patients with acute kidney injury (AKI) in the tertiary care setting in Rwanda.

Methods

A rapid cost-effectiveness analysis for patients with AKI was conducted to support prioritization. An ‘adaptive’ HTA approach was undertaken by adjusting the international Decision Support Initiative reference case for time and data constraints. Available local and international data were used to analyze the cost-effectiveness and budget impact of peritoneal dialysis (PD) compared with hemodialysis (HD) in the tertiary hospital setting.

Results

The analysis found that HD was slightly more effective and slightly more expensive in the payer perspective for most patients with AKI (aged 15–49). HD appeared to be cost-effective when only comparing these two dialysis strategies with an incremental cost-effectiveness ratio of 378,174 Rwandan francs (RWF) or 367 United States dollars (US$), at a threshold of 0.5 × gross domestic product per capita (RWF 444,074 or US$431). Sensitivity analysis found that reducing the cost of HD kits would make HD even more cost-effective. Uncertainty regarding PD costs remains.

Budget impact analysis demonstrated that reducing the cost of the biggest cost driver, HD kits, could produce significantly more savings in five years than switching to PD. Thus, price negotiations could significantly improve the efficiency of HD provision.

Conclusion

Dialysis is costly and covered by insurance in many countries for the financial protection of patients. This analysis enabled policymakers to make evidence-based decisions to improve the efficiency of dialysis provision.
The c-Abl-RACK1-FAK signaling axis promotes renal fibrosis in mice through regulating fibroblast-myofibroblast transition
Authors: Bao Qianyi , Wang Anyu , Hong Wenxuan , Wang Yushu , Li Baojie , He Lin , Yuan Xiaodong , Ma Gang
Published: April 2024

Background

Renal fibrosis is a prevalent manifestation of chronic kidney disease (CKD), and effective treatments for this disease are currently lacking. Myofibroblasts, which originate from interstitial fibroblasts, aggregate in the renal interstitium, leading to significant accumulation of extracellular matrix and impairment of renal function. The nonreceptor tyrosine kinase c-Abl (encoded by the Abl1 gene) has been implicated in the development of renal fibrosis. However, the precise role of c-Abl in this process and its involvement in fibroblast-myofibroblast transition (FMT) remain poorly understood.

Methods

To investigate the effect of c-Abl in FMT during renal fibrosis, we investigated the expression of c-Abl in fibrotic renal tissues of patients with CKD and mouse models. We studied the phenotypic changes in fibroblast or myofibroblast-specific c-Abl conditional knockout mice. We explored the potential targets of c-Abl in NRK-49F fibroblasts.

Results

In this study, fibrotic mouse and cell models demonstrated that c-Abl deficiency in fibroblasts mitigated fibrosis by suppressing fibroblast activation, fibroblast-myofibroblast transition, and extracellular matrix deposition. Mechanistically, c-Abl maintains the stability of the RACK1 protein, which serves as a scaffold for proteins such as c-Abl and focal adhesion kinase at focal adhesions, driving fibroblast activation and differentiation during renal fibrosis. Moreover, specifically targeting c-Abl deletion in renal myofibroblasts could prove beneficial in established kidney fibrosis by reducing RACK1 expression and diminishing the extent of fibrosis.

Conclusions

Our findings suggest that c-Abl plays a pathogenic role in interstitial fibrosis through the regulation of RACK1 protein stabilization and myofibroblast differentiation, suggesting a promising strategy for the treatment of CKD.
​Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction
Authors: Sun Ziyi , Yun Zhangjun , Lin Jianguo , Sun Xiaoning , Wang Qingqing , Duan Jinlong , Li Cheng , Zhang Xiaoxiao , Xu Siyu , Wang Zeqi , Xiong Xingjiang , Yao Kuiwu
Published: April 2024

Background

Ischemic heart disease is one of the leading causes of mortality worldwide, and thus calls for development of more effective therapeutic strategies. This study aimed to identify potential therapeutic targets for coronary heart disease (CHD) and myocardial infarction (MI) by investigating the causal relationship between plasma proteins and these conditions.

Methods

A two-sample Mendelian randomization (MR) study was performed to evaluate more than 1600 plasma proteins for their causal associations with CHD and MI. The MR findings were further confirmed through Bayesian colocalization, Summary-data-based Mendelian Randomization (SMR), and Transcriptome-Wide Association Studies (TWAS) analyses. Further analyses, including enrichment analysis, single-cell analysis, MR analysis of cardiovascular risk factors, phenome-wide Mendelian Randomization (Phe-MR), and protein-protein interaction (PPI) network construction were conducted to verify the roles of selected causal proteins.

Results

Thirteen proteins were causally associated with CHD, seven of which were also causal for MI. Among them, FES and PCSK9 were causal proteins for both diseases as determined by several analytical methods. PCSK9 was a risk factor of CHD (OR = 1.25, 95% CI: 1.13–1.38, P = 7.47E-06) and MI (OR = 1.36, 95% CI: 1.21–1.54, P = 2.30E-07), whereas FES was protective against CHD (OR = 0.68, 95% CI: 0.59–0.79, P = 6.40E-07) and MI (OR = 0.65, 95% CI: 0.54–0.77, P = 5.38E-07). Further validation through enrichment and single-cell analysis confirmed the causal effects of these proteins. Moreover, MR analysis of cardiovascular risk factors, Phe-MR, and PPI network provided insights into the potential drug development based on the proteins.

Conclusions

This study investigated the causal pathways associated with CHD and MI, highlighting the protective and risk roles of FES and PCSK9, respectively. FES. Specifically, the results showed that these proteins are promising therapeutic targets for future drug development.
Exosomes in the pathogenesis and treatment of cancer-related cachexia
Authors: Ru Qin , Chen Lin , Xu Guodong , Wu Yuxiang
Published: April 2024

Cancer-related cachexia is a metabolic syndrome characterized by weight loss, adipose tissue decomposition, and progressive skeletal muscle atrophy. It is a major complication of many advanced cancers and seriously affects the quality of life and survival of cancer patients. However, the specific molecules that mediate cancer-related cachexia remain elusive, and the fundamental cellular and molecular mechanisms associated with muscle atrophy and lipidolysis in cancer patients still need to be investigated. Exosomes, a newly discovered class of small extracellular vesicles that facilitate intercellular communication, have a significant role in the onset and development of various cancers. Studies have shown that exosomes play a role in the onset and progression of cancer-related cachexia by transporting active molecules such as nucleic acids and proteins. This review aimed to provide an overview of exosome developments in cancer-induced skeletal muscle atrophy and adipose tissue degradation. More importantly, exosomes were shown to have potential as diagnostic markers or therapeutic strategies for cachexia and were prospected, providing novel strategies for the diagnosis and treatment of cancer-related cachexia.
Preoperative handgrip strength can predict early postoperative shoulder function in patients undergoing arthroscopic rotator cuff repair
Authors: Liu Yu-Cheng , Huang Shu-Wei , Adams Christopher R. , Lin Chung-Ying , Chen Yu-Pin , Kuo Yi-Jie , Chuang Tai-Yuan
Published: April 2024

Background

Rotator cuff tears (RCTs) are a common musculoskeletal disorder, and arthroscopic rotator cuff repair (ARCR) is widely performed for tendon repair. Handgrip strength correlates with rotator cuff function; however, whether preoperative grip strength can predict functional outcomes in patients undergoing ARCR remains unknown. This study aimed to investigate the correlation between preoperative grip strength and postoperative shoulder function following ARCR.

Methods

A total of 52 patients with full-thickness repairable RCTs were prospectively enrolled. Baseline parameters, namely patient characteristics and intraoperative findings, were included for analysis. Postoperative shoulder functional outcomes were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) questionnaire and Constant–Murley scores (CMSs). Patients were followed up and evaluated at three and six months after ARCR. The effects of baseline parameters on postoperative outcomes were measured using generalized estimating equations.

Results

At three and six months postoperatively, all clinical outcomes evaluated exhibited significant improvement from baseline following ARCR. Within 6 months postoperatively, higher preoperative grip strength was significantly correlated with higher CMSs (β = 0.470, p = 0.022), whereas increased numbers of total suture anchors were significantly correlated with decreased CMSs (β =  − 4.361, p = 0.03). Higher body mass index was significantly correlated with higher postoperative QDASH scores (β = 1.561, p = 0.03) during follow-up.

Conclusions

Higher baseline grip strength predicts more favorable postoperative shoulder function following ARCR. A preoperative grip strength test in orthopedic clinics may serve as a predictor for postoperative shoulder functional recovery in patients undergoing ARCR.
A systematic literature review on the health-related quality of life and economic burden of Fabry disease
Authors: Jovanovic Ana , Miller-Hodges Eve , Castriota Felicia , Takyar Shweta , Howitt Heena , Ayodele Olulade
Published: April 2024

Background

Fabry disease (FD) is a rare lysosomal storage disease associated with glycolipid accumulation that impacts multiple physiological systems. We conducted a systematic literature review (SLR) to characterize the humanistic (quality of life [QoL]) and economic burden of FD.

Methods

Searches were conducted in the Embase, MEDLINE®, and MEDLINE®In-Process databases from inception to January 19, 2022. Conference abstracts of specified congresses were manually searched. Additional searches were performed in the Cochrane and ProQuest databases for the humanistic SLR and the National Health Service Economic Evaluations Database for the economic SLR. Studies of patients with FD of any sex, race, and age, and published in the English language were included. There was no restriction on intervention or comparator. For the humanistic SLR, studies that reported utility data, database/registry-based studies, questionnaires/surveys, and cohort studies were included. For the economic SLR, studies reporting economic evaluations or assessing the cost of illness and resource use were included.

Results

Of the 1363 records identified in the humanistic search, 36 studies were included. The most commonly used QoL assessments were the 36-item Short-Form Health Survey (n = 16), EQ-5D questionnaire descriptive system or visual analog scale (n = 9), and the Brief Pain Inventory (n = 8). Reduced QoL was reported in patients with FD compared with healthy populations across multiple domains, including pain, physical functioning, and depressive symptoms. Multiple variables—including sex, age, disease severity, and treatment status—impacted QoL. Of the 711 records identified in the economic burden search, 18 studies were included. FD was associated with high cost and healthcare resource use. Contributors to the cost burden included enzyme replacement therapy, healthcare, and social care. In the seven studies that reported health utility values, lower utility scores were generally associated with more complications (including cardiac, renal, and cerebrovascular morbidities) and with classical disease in males.

Conclusion

FD remains associated with a high cost and healthcare resource use burden, and reduced QoL compared with healthy populations. Integrating information from QoL and economic assessments may help to identify interventions that are likely to be of most value to patients with FD.
LOXL1-AS1 contributes to metastasis in sonic-hedgehog medulloblastoma by promoting cancer stem-like phenotypes
Authors: Do Anh Duy , Wu Kuo-Sheng , Chu Shing-Shung , Giang Le Hien , Lin Yu-Ling , Chang Che-Chang , Wong Tai-Tong , Hsieh Chia-Ling , Sung Shian-Ying
Published: April 2024

Background

Medulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve clinical outcomes. Among the four molecular subgroups, sonic-hedgehog (SHH)-MB harbors clinical and genetic heterogeneity with a subset of high-risk cases. Recently, long non-coding (lnc)RNAs were implied to contribute to cancer malignant progression, but their role in MB remains unclear. This study aimed to identify pro-malignant lncRNAs that have prognostic and therapeutic significance in SHH-MB.

Methods

The Daoy SHH-MB cell line was engineered for ectopic expression of MYCN, a genetic signature of SHH-MB. MYCN-associated lncRNA genes were identified using RNA-sequencing data and were validated in SHH-MB cell lines, MB tissue samples, and patient cohort datasets. SHH-MB cells with genetic manipulation of the candidate lncRNA were evaluated for metastatic phenotypes in vitro, including cell migration, invasion, sphere formation, and expressions of stemness markers. An orthotopic xenograft mouse model was used to evaluate metastasis occurrence and survival. Finally, bioinformatic screening and in vitro assays were performed to explore downstream mechanisms.

Results

Elevated lncRNA LOXL1-AS1 expression was identified in MYCN-expressing Daoy cells and MYCN-amplified SHH-MB tumors, and was significantly associated with lower survival in SHH-MB patients. Functionally, LOXL1-AS1 promoted SHH-MB cell migration and cancer stemness in vitro. In mice, MYCN-expressing Daoy cells exhibited a high metastatic rate and adverse effects on survival, both of which were suppressed under LOLX1-AS1 perturbation. Integrative bioinformatic analyses revealed associations of LOXL1-AS1 with processes of cancer stemness, cell differentiation, and the epithelial-mesenchymal transition. LOXL1-AS1 positively regulated the expression of transforming growth factor (TGF)-β2. Knockdown of TGF-β2 in SHH-MB cells significantly abrogated their LOXL1-AS1-mediated prometastatic functions.

Conclusions

This study proved the functional significance of LOXL1-AS1 in SHH-MB metastasis by its promotion of TGF-β2-mediated cancer stem-like phenotypes, providing both prognostic and therapeutic potentials for targeting SHH-MB metastasis.
The effect of dexmedetomidine on the postoperative recovery of patients with severe traumatic brain injury undergoing craniotomy treatment: a retrospective study
Authors: Deng Zhu , Gu Yong , Luo Le , Deng Lin , Li Yingwei , Huang Wanyong
Published: April 2024

Background

Traumatic brain injury (TBI) has been a worldwide problem for neurosurgeons. Patients with severe TBI may undergo craniotomy. These patients often require sedation after craniotomy. Dexmedetomidine (DEX) has been used in patients receiving anesthesia and in intensive care units. Not much is known about the postoperative effect of DEX in patients with severe TBIs undergoing craniotomy. The purpose of this study was to explore the effects of postoperative DEX administration on severe TBI patients who underwent craniotomy.

Methods

Patients who underwent craniectomy for severe TBI at our hospital between January 2019 and February 2022 were included in this study. The patients were admitted to the intensive care unit (ICU) after surgery to receive sedative medication. The patients were then divided into DEX and control groups. We analyzed the sedation, hemodynamics, and other conditions of the patients (hypoxemia, duration of ventilation during endotracheal intubation, whether tracheotomy was performed, and the duration in the ICU) during their ICU stay. Other conditions, such as delirium after the patients were transferred to the general ward, were also analyzed.

Results

A total of 122 patients were included in this study. Among them, 53 patients received DEX, and the remaining 69 did not. The incidence of delirium in the general ward in the DEX group was significantly lower than that in the control group (P < 0.05). The incidence of bradycardia in the control group was significantly lower than that in the DEX group (P < 0.05). Other data from the DEX group and the control group (hypotension, hypoxemia, etc.) were not significantly different (P > 0.05).

Conclusion

The use of DEX in the ICU can effectively reduce the incidence of delirium in patients who return to the general ward after craniotomy. DEX had no adverse effect on the prognosis of patients other than causing bradycardia.
Caterpillar movement mediates spatially local interactions and determines the relationship between population density and contact
Authors: Carson Brendan D. , Orians Colin M. , Crone Elizabeth E.
Published: April 2024

Background

While interactions in nature are inherently local, ecological models often assume homogeneity across space, allowing for generalization across systems and greater mathematical tractability. Density-dependent disease models are a prominent example of models that assume homogeneous interactions, leading to the prediction that disease transmission will scale linearly with population density. In this study, we examined how the scale of larval butterfly movement interacts with the resource landscape to influence the relationship between larval contact and population density in the Baltimore checkerspot (Euphydryas phaeton). Our study was inspired by the recent discovery of a viral pathogen that is transmitted horizontally among Baltimore checkerspot larvae.

Methods

We used multi-year larvae location data across six Baltimore checkerspot populations in the eastern U.S. to test whether larval nests are spatially clustered. We then integrated these spatial data with larval movement data in different resource contexts to investigate whether heterogeneity in spatially local interactions alters the assumed linear relationship between larval nest density and contact. We used Correlated Random Walk (CRW) models and field observations of larval movement behavior to construct Probability Distribution Functions (PDFs) of larval dispersal, and calculated the overlap in these PDFs to estimate conspecific contact within each population.

Results

We found that all populations exhibited significant spatial clustering in their habitat use. Subsequent larval movement rates were influenced by encounters with host plants and larval age, and under many movement scenarios, the scale of predicted larval movement was not sufficient to allow for the “homogeneous mixing” assumed in density dependent disease models. Therefore, relationships between population density and larval contact were typically non-linear. We also found that observed use of available habitat patches led to significantly greater contact than would occur if habitat use were spatially random.

Conclusions

These findings strongly suggest that incorporating larval movement and spatial variation in larval interactions is critical to modeling disease outcomes in E. phaeton. Epidemiological models that assume a linear relationship between population density and larval contact have the potential to underestimate transmission rates, especially in small populations that are already vulnerable to extinction.
Perceptions of rural and urban residents in Borana pastoral and agro-pastoral areas in Ethiopia related to milk adulteration
Authors: Amenu Kebede , Shibiru Abagena , Kumbe Adem , Konyole Silvenus Ochieng , Jaleta Megarsa Bedasa , Tiki Waktole
Published: April 2024

Milk is a nutritious food that plays a great role in the diets of a society largely dependent on livestock production. On the other hand, contaminants can enter milk naturally or intentionally, causing a negative impact on the health of consumers. Milk adulteration is a wide concern in the dairy industry in many countries, including Ethiopia, with a subsequent negative impact on its nutritive value and potentially affecting the health of consumers. This study was designed to assess the perceptions of rural and urban residents in Borana pastoral and agro-pastoral areas in Ethiopia related to milk adulteration. It was also aimed at identifying the potential reasons for milk adulteration in the area. A semi-structured questionnaire and focus group discussions (FGDs) were used to collect quantitative and qualitative data, respectively, focusing on the types of substances added to milk and the reasons for the addition of the substances. In rural and urban areas, 73.1% and 91.7% of respondents reported suspicion of the addition of nonmilk substances or milk of other animal species to cow’s milk before selling, respectively. According to the qualitative data, most reported adulterants were water and ‘pasta or rice water’ (a murky fluid left after boiling rice or pasta). Respondents mentioned that they identify adulterated milk by observation or tasting. Economic gain was the primary perceived reason to adulterate the milk according to the study participants. The respondents had concerns about the quality and safety of milk associated with adulteration in the area. The weak enforcement of regulations related to milk quality and marketing as well as the inadequacy of capacity for the detection of adulteration were mentioned as gaps toward mitigating the problems. Awareness creation about the negative impacts of milk adulteration among the community supported by strategies for regulation, such as improving regular testing of milk and taking actions on adulterated milk, is recommended to tackle consumer concerns around milk adulteration in the area.
Brood success of sex-role-reversed pheasant-tailed jacanas: the effects of social polyandry, seasonality, and male mating order
Authors: Lee Ya-Fu , Kuo Yen-Min , Chuang Bing-Yuan , Hsu Hui-Ching , Huang Yi-Jun , Su Yu-Chen , Lee Wen-Chen
Published: April 2024

Multiple mating by avian females may increase hatching and overall brood success; however, reproductive effort and parental investment are costly, and females may be gradually depleted, with lowered outputs over time. Thus, males in social polyandry systems may differ greatly in their reproductive gains. In the present study, we investigated the reproductive outputs of social polyandrous and sex-role-reversed pheasant-tailed jacanas, Hydrophasianus chirurgus, to assess the effects of polyandry, seasonality, and male mating order on breeding success. Female jacanas produced multiple clutches, either by leaving two or more clutches with an individual male (22%), or by mating with two or more males (78%). The polyandrous females laid both the first and second clutches earlier and showed a breeding period more than twice as long as that of monandrous females. Both polyandry and seasonality affected the fate of a clutch, where clutches from polyandrous females and the early season had higher hatching and brood success rates, but the number of polyandrous females declined over the season. Polyandrous females not only laid more clutches and eggs, and gained more hatchlings and fledglings, but also achieved higher per-clutch outputs and hatching rates than monandrous females. In polyandry groups, males gained higher total hatchlings and fledglings, although not total clutches or eggs, than males in monandry or bi-andry groups. Moreover, males in polyandry groups achieved higher hatchlings and fledglings per clutch and higher hatching and brood success rates. In polyandry groups, the first-mating males obtained more clutches, eggs, and hatchlings; however, they did not have higher success rates, nor total fledglings and per-clutch outputs, than males who mated later. Overall, the results indicate a selective advantage of polyandry for the jacanas studied, particularly in the early breeding season. This advantage, however, differs both between the sexes and intra-sexually, suggesting strong connections with certain ecological/environmental conditions in addition to the jacanas’ own quality.
A pivotal phase 2 single-arm study of glecirasib (JAB-21822) in patients with NSCLC harboring KRAS G12C mutation.
Authors: Shi Yuankai , Fang Jian , Xing Ligang , Yao Yu , Zhang Jian , Liu Lian , Wang Yongsheng , Hu Changlu , Xiong Jianping , Liu Zhihua , Yang Runxiang , Wang Zhen , Zhao Enfeng , Wang Mengzhao , Zhao Yanqiu , Tang Kejing , Li Zhihua , Song Zhengbo
Published: April 2024

468214

Background: KRAS G12C mutation occurs in approximately 4% of non-small cell lung cancers (NSCLC) in China. Glecirasib (Jacobio, Beijing, PRC) is a potent and highly selective covalent oral inhibitor of KRAS G12C. Methods: This phase 2 single-arm study (NCT05009329) of glecirasib was conducted in China at 43 sites, enrolling participants with locally advanced or metastatic KRAS G12C mutated NSCLC. Subjects must have received prior platinum-based therapy and an immune checkpoint inhibitor (ICI) as well as appropriate targeted agents for any actionable mutations per local standards. Primary study objective is overall response rate (ORR) assessed by independent review committee (IRC). The secondary study objectives include duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Here we report topline results from this pivotal study. Results: A total of 119 patients with NSCLC harboring KRAS G12C mutation were enrolled and treated with single agent glecirasib at 800mg daily (median follow up 10.4 months). The median age was 62 years, 79% was male and 21% was female, and 80.7% had ECOG PS 1. The prior lines of therapy include 1-3, with 94.1% (112/119) patients having received prior platinum-based therapy and ICI. Confirmed ORR was 47.9% (56/117; 95% CI, 38.5%-57.3%) and confirmed DCR was 86.3% (101/117; 95% CI, 78.7%-92%) assessed by IRC. Median PFS per IRC was 8.2 months (95% CI, 5.5 – 13.1), and median OS was 13.6 months (95% CI, 10.9 – NE). Median DOR has not been reached (95% CI, 7.2 – NE ). Overall, treatment-related adverse events (TRAEs) of any grade were observed in 97.5% of subjects. Most common TRAEs [≥15%] were anemia (56.3%), blood bilirubin increased (48.7%), alanine aminotransferase increased (35.3%), aspartate aminotransferase increased (35.3%), hypertriglyceridemia (28.6%) and γ-Glutamyl transferase increased (15.1%). Grade 3 and 4 TRAEs were observed in 39.5%. No grade 5 TRAEs occurred. Most of patients can stay on the treatment and 5.0% patients discontinued the treatment due to TRAE. In contrast to other FDA approved KRAS G12C inhibitor, Gleciasib has 6.7% of nausea, 7.6% vomiting, 3.4% diarrhea in which only one grade 3 nausea is reported. Conclusion: The pivotal phase 2 study of Glecirasib has met the primary endpoints and demonstrates impressive ORR and PFS with promising clinical activity for patients with KRAS G12C mutated advanced NSCLC. Glecirasib is well tolerated, with an extremely low gastrointestinal toxicity profile, which may improve patient compliance with oral therapy. Clinical trial information: NCT05009329 .
The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study
Authors: Eriksen Rebeca , White Margaret C , Dawed Adem Y , Perez Isabel Garcia , Posma Joram M , Haid Mark , Sharma Sapna , Prehn Cornelia , Thomas E Louise , Koivula Robert W , Bizzotto Roberto , Mari Andrea , Giordano Giuseppe N , Pavo Imre , Schwenk Jochen M , De Masi Federico , Tsirigos Konstantinos D , Brunak Søren , Viñuela Ana , Mahajan Anubha , McDonald Timothy J , Kokkola Tarja , Rutters Femke , Beulens Joline , Muilwijk Mirthe , Blom Marieke , Elders Petra , Hansen Tue H , Fernandez-Tajes Juan , Jones Angus , Jennison Chris , Walker Mark , McCarthy Mark I , Pedersen Oluf , Ruetten Hartmut , Forgie Ian , Holst Jens J , Thomsen Henrik S , Ridderstråle Martin , Bell Jimmy D , Adamski Jerzy , Franks Paul W , Hansen Torben , Holmes Elaine , Frost Gary , Pearson Ewan R
Published: April 2024

Context

The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.

Objective

We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.

Methods

We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D.

Results

Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes.

Conclusion

These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D.
Creating Moves to Opportunity: Experimental Evidence on Barriers to Neighborhood Choice
Authors: Bergman Peter , Chetty Raj , DeLuca Stefanie , Hendren Nathaniel , Katz Lawrence F. , Palmer Christopher
Published: April 2024

Low-income families often live in low-upward-mobility neighborhoods. We study why by using a randomized trial with housing voucher recipients that provided information, financial support, and customized search assistance to move to high-opportunity neighborhoods. The treatment increased the fraction moving to high-upward-mobility areas from 15 to 53 percent. A second trial reveals this treatment effect is driven primarily by customized search assistance. Qualitative interviews show that the intervention relaxed bandwidth constraints and addressed family-specific needs. Our findings imply many low-income families do not have strong preferences to stay in low-opportunity areas and that barriers in housing search significantly increase residential segregation by income. (JEL D83, G51, R21, R23, R31, R38)
Οι οικισμοί της Πελοποννήσου στα χρόνια της Ελληνικής Επανάστασης
Authors: Φέστας Μιχαήλ
Published: April 2024

Η διδακτορική διατριβή εξετάζει τη γεωγραφική κατανομή των οικισμών και του πληθυσμού της Πελοποννήσου στα χρόνια της Ελληνικής Επανάστασης. Με αφετηρία το τέλος της Επανάστασης, η εργασία διερευνά εάν η σχετική εικόνα που προκύπτει αναφορικά με την οικιστική και πληθυσμιακή συγκρότηση του πελοποννησιακού χώρου την περίοδο αυτή, προκύπτει κατά κύριο λόγο ως αποτέλεσμα ενός δεκαετούς πολέμου που μόλις είχε προηγηθεί ή εγγράφεται σε ευρύτερα, ως προς το είδος και τη χρονική τους διάρκεια, ερμηνευτικά φαινόμενα. Για να απαντηθεί το κεντρικό ερώτημα πραγματοποιήθηκε συστηματική ταύτιση και χαρτογραφική αποτύπωση περίπου 1.800 τοπωνυμίων που συμπεριλαμβάνονται στις πληθυσμιακές καταγραφές που πραγματοποίησε στο διάστημα 1828-1830 η καποδιστριακή διοίκηση, καθώς και στο αντίστοιχο υλικό που συγκέντρωσε η Γαλλική Επιστημονική Αποστολή της Πελοποννήσου. Παράλληλα, η έρευνα αξιοποίησε ένα μεγάλο πλήθος γραπτών πηγών (απογραφικών και μη), αλλά και χωρικών. Μέσα από την επεξεργασία του υλικού, την ποσοτική ανάλυση των δεδομένων και ένα πλήθος πρωτότυπων θεματικών χαρτών που δημιουργήθηκαν από το συγγραφέα με τη χρήση Συστημάτων Γεωγραφικών Πληροφοριών (GIS), η έρευνα ανασυστήνει συστηματικά και σε βάθος τον οικιστικό χάρτη της Πελοποννήσου την περίοδο αυτή και παράλληλα αναλύει ζητήματα που σχετίζονται με τη διοικητική γεωγραφία του ελληνικού χώρου, το βαθμό αξιοπιστίας των πηγών που διαθέτουμε για τον πληθυσμό την περίοδο αυτή και τέλος με τους μετασχηματισμούς που γνωρίζει το οικιστικό δίκτυο και η κατανομή του πληθυσμού στο χώρο στη μακρά διάρκεια.
Επίδραση πρόσθετων νανοτεχνολογίας στην ανθεκτικότητα του οπλισμένου τσιμεντοκονιάματος
Authors: Παναγιωτακοπούλου Χριστίνα
Published: April 2024

Το αντικείμενο της παρούσας διατριβής είναι η πειραματική μελέτη και διερεύνηση της ανθεκτικότητας δοκιμίων τσιμεντοκονιάματος στα οποία προστέθηκαν νανοσωλήνες και νανοΐνες άνθρακα σε ποσοστό 0,1 % κ.β τσιμέντου. Συγκεκριμένα, έγινε συνολική ανασκόπηση των υλικών που χρησιμοποιήθηκαν για την παρασκευή των δοκιμίων τσιμεντοκονιάματος, και αναπτύχθηκαν αναλυτικά οι πρώτες ύλες, τα είδη, οι ιδιότητες, οι παράγοντες που τα επηρεάζουν και οι τρόποι παρασκευής τους. Επίσης, παρουσιάστηκε η έννοια της ανθεκτικότητας των δομικών στοιχείων από τσιμεντοκονίαμα και αναλύθηκαν οι παράγοντες που επιδρούν σε αυτήν. Στην συνέχεια αναλύθηκαν οι παράγοντες που συντελούν στην διάβρωση του οπλισμού και παρουσιάστηκαν αναλυτικά τα είδη της διάβρωσης και οι μέθοδοι προστασίας του οπλισμού έναντι αυτής. Τα υλικά νανοτεχνολογίας, νανοΐνες και νανοσωλήνες άνθρακα προστέθηκαν σε δοκίμια τσιμεντοκονιάματος με εγκιβωτισμένο σιδηρό οπλισμό. Συγκεκριμένα, εκτός από τα δοκίμια αναφοράς (Κατηγορία Ι) εξετάστηκαν άλλες δύο (2) κατηγορίες δοκιμίων τσιμεντοκονιάματος στα οποία προστέθηκαν νανοσωλήνες άνθρακα (Κατηγορία ΙΙ) σε ποσοστό 0,1 % κ.β τσιμέντου και νανοΐνες άνθρακα (Κατηγορία ΙΙΙ) σε ποσοστό 0,1 % κ.β τσιμέντου. Η επίδραση των ανωτέρω πρόσθετων υλικών νανοτεχνολογίας στην ανθεκτικότητα των τσιμεντοκονιαμάτων εκτιμήθηκε με τις ακόλουθες μεθόδους: •Μέτρηση του δυναμικού διάβρωσης στον οπλισμό συναρτήσει του χρόνου •Μέτρηση του ρεύματος διάβρωσης στον οπλισμό συναρτήσει του χρόνου •Μέτρηση απώλειας μάζας του οπλισμού λόγω διάβρωσης, μέσω της ηλεκτροχημικής και βαρυμετρικής μεθόδου. •Μέτρηση της περιεκτικότητας των ολικών χλωριόντων στο τσιμεντοκονίαμα •Έλεγχος της ποιότητας της δομής των δειγμάτων τσιμεντοκονιάματος μέσω της ηλεκτρονικής μικροσκοπίας σάρωσης (Scanning Electron Microscopy, SEM),και αντίστοιχα ποσοτική ανάλυση μέσω του μικροσκοπίου. •Έλεγχος της μικροδομής των δειγμάτων τσιμεντοκονιάματος μέσω της φασματοσκοπίας περίθλασης ακτίνων Χ (XRD)Από τα πειραματικά αποτελέσματα προέκυψε ότι η προσθήκη νανοσωλήνων και νανοϊνών άνθρακα, σε ποσοστό όπως εμφανίζεται στην παρούσα εργασία, αυξάνει την ανθεκτικότητα των εξεταζόμενων δοκιμίων τσιμεντοκονιάματος. Πιο συγκεκριμένα τα δοκίμια στα οποία έχουν προστεθεί νανοΐνες άνθρακα εμφανίζουν μεγαλύτερη ανθεκτικότητα από τα δοκίμια αναφοράς αλλά και από τα δοκίμια που έχουν προστεθεί νανοσωλήνες άνθρακα.