bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical analysis of load distribution in porcine hip joints at different acetabular coverages
Authors: Tachibana Tetsuya , Katagiri Hiroki , Matsuda Junpei , Ozeki Nobutake , Watanabe Toshifumi , Sekiya Ichiro , Jinno Tetsuya
Published: July 2024

Background

Developmental dysplasia of the hip causes secondary osteoarthritis. Finite element analysis suggests high hip joint contact pressure in patients with hip dysplasia and a reduction in contact pressure after periacetabular osteotomy. However, few biomechanical studies have examined the load distribution in the hip joint. This study aimed to investigate the biomechanical properties of load distribution in porcine hip joints at different acetabular coverages.

Methods

Six porcine hip joints were analyzed using three models: 1) neutral coverage, 2) 15° under-coverage (defined as dysplasia model), and 3) 15° over-coverage created by varying the acetabular coverage. The load distribution was assessed using a pressure-mapping sensor system after applying a loading force of 100 N to the hip joint.

Results

In the dysplasia model, the load was concentrated at the acetabular rim; in the neutral and over-coverage models, it was dispersed. The average contact pressure was significantly higher in the dysplasia model than in the neutral coverage model ([0.42 vs. 0.3 MPa]; p = 0.004). The contact area was significantly smaller in the dysplasia model than in the neutral coverage model ([250.7 vs. 345.0 mm2]; p = 0.004). No significant differences were observed in contact pressure or area between the neutral and over-coverage models.

Conclusions

Insufficient acetabular coverage in the dysplasia model demonstrated higher contact pressure and smaller contact area than the neutral model. Conversely, the contact pressure and area in the over-coverage model did not differ significantly from those in the normal model. Therefore, surgeons should note that acetabular coverage overcorrection has limited effect; normalization is crucial during periacetabular osteotomy.
Crosstalk between skeletal muscle ratio and cholesterol metabolism disorders: a cross-section study
Authors: Wang Yunle , Hu Jun , Shen Hui , Liu Chunxing , Yang Lijuan
Published: July 2024

Background

Dysfunction of cholesterol metabolism may be associated with low skeletal muscle mass.  This study aimed to explore the relationship between skeletal muscle mass and cholesterol metabolic disorders in adults.

Methods

The data of a total of 5949 people with complete medical history data, biochemical data and body composition analysis were recruited. According to the serum cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and nonHDL, the population was divided into a disorder group and a normal group. Independent sample t tests, chi-square tests, Pearson's correlation analyses and binary logistic regression analyses were used to study the effect of body composition on abnormal cholesterol metabolism. According to BMI and sex, the population was divided into different subgroups, and binary logistic regression analysis was used to study the effect of the skeletal mass ratio on cholesteral metabolic disorders in different subgroups.

Results

There were significant differences in sex, alcohol consumption, body weight, BMI, skeletal muscle mass index (SMI) [total skeletal muscle mass (kg)/height 2 (m2)] and skeletal muscle mass ratio (SMR) [total skeletal muscle mass (kg)/weight (kg) *100] between the disorder group (hypercholesterolemia, hyper-LDL, lower-HDL and hyper-nonHDL) and the normal group. Pearson correlation analysis revealed that the SMR was negatively correlated, while the SMI was positively correlated with cholesterol metabolic disorders in both sexes. The overweight group was older and had a greater SMI, abnormal cholesteral metabolism ratio and lower SMR than the normal-weight group. In the normal-weight group, the SMR was an independent protective factor against different kinds of cholesteral metabolic disorders in both sexes, while the SMI was a risk factor. In the overweight subgroup, the protective effect on HDL and nonHDL metabolism remained in the male subgroup but disappeared in the female subgroup. However, the SMI was an independent risk factor for different kinds of cholesteral metabolic disorders in both sexes.

Conclusions

SMR was an independent protective factor against cholesterol metabolic disorders in both males and females, especially in the normal weight group. SMI was an independent risk factor, especially in the overweight group.
Sclerotherapy for the intraoral ranula with bleomycin: technical considerations and preliminary experience
Authors: Zhang Hong-Yu , Su Li-Wen , Sun Huan , Rui Chao-Chen , Wu Yang
Published: July 2024

Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment.
Oncologists’ palliative care referral behaviour: testing utility of social exchange theory as an explanatory framework
Authors: Salins Naveen , Hughes Sean , Preston Nancy
Published: July 2024

Background

Adults and children with cancer are referred to palliative care infrequently or late. Oncologists often gatekeep these referrals. Social exchange theory is used to explain physician referral behaviour in various clinical settings. Its utility in a cancer palliative care setting is not known.

Methods

We used Karl Popper’s hypothetico-deductive approach to test the hypothesis. The hypothesis was that social exchange theory is a helpful framework for explaining oncologists’ palliative care referral behaviour in a cancer setting. The utility of the theoretical framework was tested against the empiric findings of a systematic review and original research.

Results

Most components of social exchange theory known to explain physician referral behaviour like beliefs about the provider or service, emotions triggered during the professional engagement, its symbolism and stigma, the complexity of the referral task, efforts needed to achieve it, its cost, benefit, and value were similar in a cancer setting. Empirical findings suggest that oncologists provided strategies and solutions to better palliative care integration instead of comparing their existing engagement with potential alternatives and choosing them.

Conclusion

Social exchange theory was found to be helpful in explaining oncologists’ palliative care referral behaviour. To further develop the social exchange theory based on the data used to test it, it is recommended to include feedback and solutions as a component of the theoretical framework alongside a comparison level for alternatives.
A pseudonymized corpus of occupational health narratives for clinical entity recognition in Spanish
Authors: Dunstan Jocelyn , Vakili Thomas , Miranda Luis , Villena Fabián , Aracena Claudio , Quiroga Tamara , Vera Paulina , Viteri Valenzuela Sebastián , Rocco Victor
Published: July 2024

Despite the high creation cost, annotated corpora are indispensable for robust natural language processing systems. In the clinical field, in addition to annotating medical entities, corpus creators must also remove personally identifiable information (PII). This has become increasingly important in the era of large language models where unwanted memorization can occur. This paper presents a corpus annotated to anonymize personally identifiable information in 1,787 anamneses of work-related accidents and diseases in Spanish. Additionally, we applied a previously released model for Named Entity Recognition (NER) trained on referrals from primary care physicians to identify diseases, body parts, and medications in this work-related text. We analyzed the differences between the models and the gold standard curated by a physician in detail. Moreover, we compared the performance of the NER model on the original narratives, in narratives where personal information has been masked, and in texts where the personal data is replaced by another similar surrogate value (pseudonymization). Within this publication, we share the annotation guidelines and the annotated corpus.
Novel transcriptional regulation of the GAP promoter in Pichia pastoris towards high expression of heterologous proteins
Authors: Lin Xiangna , Ding Weiqiu , Zheng Shaoyan , Wu Lianna , Chen Xue , Xie Chunfang , Liu Daling , Yao Dongsheng
Published: July 2024

Background

Pichia pastoris (Komagataella phaffii) is a promising production host, but the usage of methanol limits its application in the medicine and food industries.

Results

To improve the constitutive expression of heterologous proteins in P. pastoris, four new potential transcription regulators (Loc1p, Msn2p, Gsm1p, Hot1p) of the glyceraldehyde triphosphate dehydrogenase promoter (pGAP) were revealed in this study by using cellulase E4 as reporter gene. On this basis, a series of P. pastoris strains with knockout or overexpression of transcription factors were constructed and the deletion of transcription factor binding sites on pGAP was confirmed. The results showed that Loc1p and Msn2p can inhibit the activity of pGAP, while Gsm1p and Hot1p can enhance the activity of pGAP; Loc1p, Gsm1p and Hot1p can bind directly to pGAP, while Msn2p must be treated to expose the C-terminal domain to bind to pGAP. Moreover, manipulating a single transcription factor led to a 0.96-fold to 2.43-fold increase in xylanase expression. In another model protein, aflatoxin oxidase, knocking out Loc1 based on AFO-∆Msn2 strain resulted in a 0.63-fold to 1.4-fold increase in expression. It can be demonstrated that the combined use of transcription factors can further improve the expression of exogenous proteins in P. pastoris.

Conclusion

These findings will contribute to the construction of pGAP-based P. pastoris systems towards high expression of heterologous proteins, hence improving the application potential of yeast.
The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway
Authors: Zhu Yu-Heng , Jia Qin-Yuan , Yao Hong-Fei , Duan Zong-Hao , Ma Xue-Shi-Yu , Zheng Jia-Hao , Yin Yi-Fan , Liu Wei , Zhang Jun-Feng , Hua Rong , Ma Ding , Sun Yong-Wei , Yang Jian-Yu , Liu De-Jun , Huo Yan-Miao
Published: July 2024

Background

This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC).

Methods

LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo.

Results

LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo.

Conclusions

Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.
EBP1 promotes the malignant biological behaviors of kidney renal clear cell carcinoma through activation of p38/HIF-1α signaling pathway
Authors: Meng Huan , Cao Shuxia , Tian Shengri , Huo Jiaqi , Li Xiangdan , Xu Dongyuan , Liu Lan
Published: July 2024

Background

Kidney Renal Clear Cell Carcinoma (KIRC) is a common malignant tumor of the urinary system, and its incidence is increasing. ERBB3 binding protein (EBP1) is upregulated in various cancers. However, the connection between EBP1 and KIRC has not been reported.

Methods

The expression of EBP1 in normal kidney tissue and KIRC tissue was analyzed through database and tissue microarray. EBP1 was knocked down in KIRC cell lines, and its impact on KIRC proliferation was assessed through CCK-8, soft agar assay, and flow cytometry. Scratch and transwell assays were used to evaluate the influence of EBP1 on KIRC invasion and migration. Nude mice tumor experiment were conducted to examine the effect of EBP1 on tumor tissue. Database analysis explored potential pathways involving EBP1, and validation was performed through Western blot experiments and p38 inhibitor.

Results

EBP1 is upregulated in KIRC and significantly correlates with clinical staging, pathological grading, and lymph node metastasis in patients. The mechanism research showed that knocking down EBP1 inhibited KIRC proliferation, invasion, and migration and inhibited p38 phosphorylation and the expression of hypoxia-inducible factor-1α (HIF-1α) in KIRC. p-38 inhibitor (SB203580) inhibits p38 phosphorylation and HIF-1α expression and suppresses cell viability in a concentration-dependent manner, but has no effect on EBP1 expression. HEK 293T cells overexpressing EBP1 showed increased expression of phosphorylated p38 and HIF-1α and enhanced cell viability, however, SB203580 inhibited this effect of EBP1.

Conclusion

EBP1 may promote the occurrence and development of KIRC by regulating the expression of p38/HIF-1α signaling pathway.

Graphical Abstract
Histogenetic insights and genetic landscape of fibromatosis-like undifferentiated gastric carcinoma: a focused study
Authors: Wang Yang-Kun , Wang Su-Nan , Liao Xing-Hai , Wang Zhi-Qiang , Li Ping , Yun Tian , Meng De-Qi
Published: July 2024

Background

The aim of this study was to elucidate the histogenesis and genetic underpinnings of fibromatosis-like undifferentiated gastric carcinoma (FLUGC), a rare pathological entity.

Method

Through a detailed analysis of seven cases, including histopathological evaluation, CTNNB1 gene mutation screening, human epidermal growth factor receptor 2 (HER2) protein level quantification, and HER2 gene amplification assessment to identify the pathological and molecular characteristics of FLUGC.

Results

Of the seven patients in this study, five were male and two were female (age: 39–73 years). Four patients presented with lesions in the gastric antrum and three had lesions in the lateral curvature of the stomach. Histopathologically, over 90% of the tumor consisted of aggressive fibromatosis-like tissue, including proliferating spindle fibroblasts and myofibroblasts and varying amounts of collagenous fibrous tissues. Undifferentiated cancer cells, accounting for less than 10%, were dispersed among the aggressive fibromatosis-like tissues. These cells were characterized by their small size and were relatively sparse without glandular ducts or nested mass-like structures. Immunophenotyping results showed positive expression of CKpan, CDX2, villin, and p53 in undifferentiated cancer cells; positive expression of vimentin in aggressive fibromatosis-like tissue; positive cytoplasmic expression of β-catenin; and focal cytoplasmic positive expression of smooth muscle actin (SMA). Genetic analysis did not reveal any mutations in the CTNNB1 gene test, nor was there amplification in the HER2 gene fluorescence in situ hybridization (FISH) test. Additionally, the Epstein-Barr encoding region (EBER) of in situ hybridization was negative; and the mismatch repair (MMR) protein was positive. Programmed cell death-1 (PD-1) was < 1–5%; programmed cell death ligand 1 (PD-L1): TPS = 1–4%, CPS = 3–8.

Conclusion

The study highlights the significance of CTNNB1, HER2, EBER, and MMR as pivotal genetic markers in FLUGC, underscoring their relevance for diagnosis and clinical management. The rarity and distinct pathological features of FLUGC emphasize the importance of accurate diagnosis to prevent underdiagnosis or misdiagnosis and to raise awareness within the medical community.
Heat stress induced piRNA alterations in pachytene spermatocytes and round spermatids
Authors: Mehta Poonam , Sethi Shruti , Yadav Santosh Kumar , Gupta Gopal , Singh Rajender
Published: July 2024

Background

Spermatogenesis is a temperature-sensitive process, and elevation in temperature hampers this process quickly and significantly. We studied the molecular effects of testicular heating on piRNAs and gene expression in rat testicular germ cells.

Methods

We generated a cryptorchid rat model by displacing the testis from the scrotal sac (34 °C) to the abdominal area (37 °C) and sacrificed animals after 1 day, 3 days, and 5 days. Pachytene spermatocytes and round spermatids were purified using elutriation centrifugation and percoll gradient methods. We performed transcriptome sequencing in pachytene spermatocytes and round spermatids to identify differentially expressed piRNAs and their probable targets, i.e., TE transcripts and mRNAs.

Results

As a result of heat stress, we observed significant upregulation of piRNAs and TE transcripts in testicular germ cells. In addition to this, piRNA biogenesis machinery and heat shock proteins (Hsp70 and Hsp90 family members) were upregulated. mRNAs have also been proposed as targets for piRNAs; therefore, we shortlisted certain piRNA-mRNA pairs with an inverse relationship of expression. We observed that in testicular heat stress, the heat shock proteins go hand-in-hand with the upregulation of piRNA biogenesis machinery. The dysregulation of piRNAs in heat-stressed germ cells, increased ping-pong activity, and disturbed expression of piRNA target transcripts suggest a connection between piRNAs, mRNAs, and TE transcripts.

Conclusions

In heat stress, piRNAs, piRNA machinery, and heat shock proteins are activated to deal with low levels of stress, which is followed by a rescue approach in prolonged stressaccompained by high TE activity to allow genetic mutations, perhaps for survival and adaptability.
Unveiling viewpoints on national food environment policies in the Dutch newspaper discourse: an interpretative media content analysis
Authors: Droog Nine M. S. , Dijkstra Coosje S. , van Selm Naomi , Poelman Maartje P. , Mackenbach Joreintje D.
Published: July 2024

Background

National food environment policies can contribute to the reduction of diet-related non-communicable diseases. Yet, their implementation in the Netherlands remains low. It has been hypothesized that the media can play a pivotal role in inducing spikes in policy attention, thereby shaping political action. The aim of this study was to examine the discourse on food policies in Dutch newspaper articles between 2000–2022, by analyzing arguments used by various actors.

Methods

A systematic search in Nexis Uni was used to identify newspaper articles that covered national-level Dutch food environment policies published in seven Dutch national newspapers between 2000–2022. Covered policies were classified into six domains including food composition, labeling, promotion, prices, provision and retail and into the four stages of the policy cycle; policy formulation, decision-making, implementation, and evaluation. A grey literature search was used to identify food policies implemented during 2000–2022. Descriptive statistics were used to summarize coverage of policies over time, policy type and policy stage. An interpretive content analysis was performed on a random subsample of the newspaper articles to determine the actors, viewpoints and arguments of the food policies.

Results

We identified 896 relevant newspaper articles. The coverage of food policies in newspapers was initially low but peaked in 2018/2021/2022. Through grey literature search we identified 6 food policies which were implemented or adjusted between 2000–2022. The majority of the newspaper articles reported on food pricing policies and were discussed in the policy formulation stage. Academics (mainly supportive) were the most and food industry (mostly opposing) the least cited actors. Supportive arguments highlighted health consequences, health inequalities and collective responsibility, whereas opposing arguments focused on unwanted governmental interference and ineffectiveness of policies.

Conclusions

Dutch newspaper articles covering food policies represented a variety of actors and arguments, with individual versus collective responsibility for food choices playing a central role in the arguments. These insights may serve as a basis for further research into why certain arguments are used and their effect on policy attention and implementation.
The vast majority of somatic mutations in plants are layer-specific
Authors: Goel Manish , Campoy José A. , Krause Kristin , Baus Lisa C. , Sahu Anshupa , Sun Hequan , Walkemeier Birgit , Marek Magdalena , Beaudry Randy , Ruiz David , Huettel Bruno , Schneeberger Korbinian
Published: July 2024

Background

Plant meristems are structured organs consisting of distinct layers of stem cells, which differentiate into new plant tissue. Mutations in meristematic layers can propagate into large sectors of the plant. However, the characteristics of meristematic mutations remain unclear, limiting our understanding of the genetic basis of somaclonal phenotypic variation.

Results

Here, we analyse the frequency and distribution of somatic mutations in an apricot tree. We separately sequence the epidermis (developing from meristem layer 1) and the flesh (developing from meristem layer 2) of several fruits sampled across the entire tree. We find that most somatic mutations (> 90%) are specific to individual layers. Interestingly, layer 1 shows a higher mutation load than layer 2, implying different mutational dynamics between the layers. The distribution of somatic mutations follows the branching of the tree. This suggests that somatic mutations are propagated to developing branches through axillary meristems. In turn, this leads us to the unexpected observation that the genomes of layer 1 of distant branches are more similar to each other than to the genomes of layer 2 of the same branches. Finally, using single-cell RNA sequencing, we demonstrate that layer-specific mutations were only transcribed in the cells of the respective layers and can form the genetic basis of somaclonal phenotypic variation.

Conclusions

Here, we analyse the frequency and distribution of somatic mutations with meristematic origin. Our observations on the layer specificity of somatic mutations outline how they are distributed, how they propagate, and how they can impact clonally propagated crops.
Association of psoriasis with allergic multimorbidity of asthma, rhinitis, and eczema among adolescents: a cross-sectional study
Authors: Ziyab Ali H. , Ali Yaser , Zein Dina , Al-Kandari Manal , Holloway John W. , Karmaus Wilfried
Published: July 2024

Background

Associations between psoriasis and allergic diseases (asthma, rhinitis, and eczema) in children have been reported in a limited number of studies, and the association between psoriasis and multimorbidity (co-occurrence) of allergic diseases remains unclear. Hence, this study aimed to assess the association between psoriasis and the co-occurrence of asthma, rhinitis, and eczema in adolescents.

Methods

This school-based cross-sectional study enrolled adolescents (n = 3,864) aged 11–14 years. Parents completed a questionnaire on doctor-diagnosed psoriasis as well as symptoms and clinical history of asthma, rhinitis, and eczema. Eight nonoverlapping groups comprising single and co-occurring current (past 12 months) asthma, rhinitis, and eczema were identified. A multinomial logistic regression model was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI).

Results

In the analytical sample (n = 3,710; 1,641 male and 2,069 female participants), 3.5% reported doctor-diagnosed psoriasis, and 15.7%, 15.0%, and 10.3% had current asthma, rhinitis, and eczema symptoms, respectively. Doctor-diagnosed psoriasis was associated with “asthma only” (aOR = 2.11, 95% CI: 1.15–3.89), “eczema only” (6.65, 4.11–10.74), “asthma + eczema” (5.25, 2.36–11.65), “rhinitis + eczema” (3.60, 1.07–12.15), and “asthma + rhinitis + eczema” (7.38, 2.93–18.58). Doctor-diagnosed psoriasis was not statistically significantly associated with “rhinitis only” (1.42, 0.71-–2.84) and “asthma + rhinitis” (1.78, 0.69–4.56).

Conclusion

Our findings indicate that psoriasis is associated with the co-occurrence of allergic diseases among adolescents. However, further studies are required to investigate which biological mechanisms may be shared between psoriasis and allergic diseases.
Barriers to HPV vaccine series completion among a predominantly hispanic border population: a mixed method evaluation
Authors: Hernandez Amir , Calderón-Mora Jessica , Lara Hatty , Drury Nicole , Molokwu Jennifer
Published: July 2024

Background

Human Papillomavirus (HPV) infections are the most common sexually transmitted infections in the United States. The HPV vaccine is a vital tool to prevent against several cancers, namely cervical cancer. Unfortunately, the uptake of the HPV vaccine among Hispanics is relatively low. Some barriers to uptake include language barriers, cultural taboos, and cost.

Purpose

This study aims to explore barriers to HPV vaccination in a predominantly Hispanic US-Mexico border county between June 2015 and March 2018.

Methods

A mixed-method approach was used to analyze covariates associated with HPV vaccine uptake and to evaluate barriers to HPV vaccination from participant follow-up calls or reminder notes.

Results

The total number of participants was 1,787. Young adults were less likely to complete the vaccination series than those aged 9-17, while individuals born in Mexico were more likely to do so. Failure to contact was the most common barrier (n=1,801, 86.42%), followed by scheduling concerns (n=99, 4.5%), being ineligible (74, 3.55%), completing series outside of the program (40, 1.92%), having medical concerns (36, 1.73%), and other reasons (34, 1.63%).

Conclusion

We predominantly identified structural barriers and various health-related determinants regarding healthcare access and quality.
Enabling radical and potentially disruptive innovations through interdisciplinarity: challenges and practices in industrial companies
Authors: Schimpf Sven , Weber Hanno , Gerlach Thomas
Published: July 2024

The motivation behind this paper and the underlying research is to shed light on how companies deal with interdisciplinary innovation activities, especially looking at the development of radical and potentially disruptive innovations. This includes the analysis of methods, processes, and organizational structures applied to support interdisciplinary innovation activities as well as challenges faced. Whereas this thematic field has been widely investigated for academic institutions and, in companies on a team level, there is only a little information on industrial companies’ current state. This understanding is especially important as shortening development cycles, and technological convergence combined with intersectoral innovations might lead to increases in radical and potentially disruptive innovations and thereby create the need for improved methods and structures throughout the innovation process. To gain insights into challenges and current practices of interdisciplinary collaboration in innovation activities, semi-structured exploratory interviews were carried out with representatives from seven industrial companies. Among others, the results of the study revealed that whereas many methodologies are said to support interdisciplinary innovation activities, a wide majority of these methodologies are applied for other reasons which make supporting interdisciplinarity seem like a kind of byproduct.
Exploring biomarkers for diagnosing and predicting organ dysfunction in patients with perioperative sepsis: a preliminary investigation
Authors: Jiang Linghui , Chen Shiyu , Li Shichao , Wang Jiaxing , Chen Wannan , Shi Yuncen , Xiong Wanxia , Miao Changhong
Published: July 2024

Objective

Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients.

Method

This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models.

Results

Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843–0.954) and good calibration.

Conclusion

Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction.

Trial registration

The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.
Dorsal raphe nucleus–hippocampus serotonergic circuit underlies the depressive and cognitive impairments in 5×FAD male mice
Authors: Chen Meiqin , Wang Chenlu , Lin Yinan , Chen Yanbing , Xie Wenting , Huang Xiaoting , Zhang Fan , Fu Congrui , Zhuang Kai , Zou Tingting , Can Dan , Li Huifang , Wu Shengxi , Luo Ceng , Zhang Jie
Published: July 2024

Background

Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression.

Methods

We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model.

Results

We found that the activity of dorsal raphe nucleus serotonin neurons (DRN5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT-dCA1CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT-dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1BR) and 4 (5-HT4R). Pharmacological activation of 5-HT1BR or 5-HT4R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT-dCA1CaMKII neural circuit to improve synaptic plasticity.

Conclusions

These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.
Cheating in online assessment: a qualitative study on reasons and coping strategies focusing on EFL teachers’ perceptions
Authors: Jalilzadeh Kaveh , Rashtchi Mojgan , Mirzapour Fatemeh
Published: July 2024

A challenging aspect of online education is assessment since academic integrity could be violated due to students’ cheating behaviors. The current qualitative research investigated English teachers’ perceptions of why students cheat in online assessments. Besides, it attempted to find strategies to reduce cheating in online assessments. Twelve teachers (seven males and five females) with at least 5 years of teaching experience in different high schools in Tabriz, Iran, participated in the study. Data were collected through semi-structured interviews and were analyzed using MAXQDA version 2022. Freedom in the absence of an invigilator, unpreparedness for assessment, getting better grades/outcomes, low self-esteem/self-confidence, shortage of time/poor time management, peer influence or competition, not taking assessment seriously, fear of failure/bad assessment outcomes, and lack of respect for academic rules/the teacher were some reasons of cheating in online assessment revealed by the analysis of the data. The teachers suggested strategies to curb cheating in online assessment, such as randomizing questions, using open-ended and essay-format questions, designing different test methods and question types, restricting exam time, designing learner-specific questions, showing one question at a time, and providing clear exam instructions. The study has some pedagogical implications for faculty members and administrators.
Chemical analysis of fragments of glass and ceramic ware from Tycho Brahe’s laboratory at Uraniborg on the island of Ven (Sweden)
Authors: Rasmussen Kaare Lund , Grinder-Hansen Poul
Published: July 2024

In addition to his astronomical observations the famous Renaissance astronomer Tycho Brahe (1546–1601) was known also for his interest in alchemy. He equipped his castle Uraniborg on the island of Ven with a state-of-the-art alchemical laboratory when it was erected around 1580. After Brahe’s death Uraniborg was demolished upon a royal decree from 1601, a process which was completed around 1650. In the present study we have analysed four glass shards and one ceramic shard most likely from the alchemical laboratory and retrieved during an archaeological excavation in 1988–90. Cross sections of the shards have been analysed for 31 trace elements by Laser Ablation Inductively Coupled Plasma with Mass Spectrometry with the aim of detecting any traces of the chemical substances on the inside or outside of the shards used in the laboratory. Four of the elements found in excess on the exterior surfaces of the shards, Cu, Sb, Au, and Hg, are in accordance with the reconstructed recipes of the three Paracelsian medicines for which Brahe was famous—Medicamenta tria. This is the first experimental data casting light on the alchemical experiments that took place at Uraniborg 1580–1599.
Chemiluminescence method for evaluating photooxidative degradation of dispensed drugs: a potential new drug information tool
Authors: Murai Yuriko , Kudo Kasumi , Suzuki Hiroyuki , Konno Taisuke , Agatsuma Yasuyuki , Nakamura Hitoshi
Published: July 2024

Background

Dispensed drugs stored by patients are often in single-dose packages (SDPs) or are crushed and mixed after being removed from a press-through package (PTP) sheet. Information on their stability is extremely limited. To address this, we explored using chemiluminescence (CL) measurements to detect oxidative degradation.

Methods

Eight amlodipine, 14 telmisartan, and two warfarin preparations were used as specimens. These preparations were stored at room temperature under various conditions, after which CL was measured. Cellopoly packaging paper was used for SDP. Three light conditions were used (Condition A: darkness, Condition B: indoor diffused light (approximately 400 lx), and Condition C: exposure to 4,000 lx). CL cumulative light output was measured every minute under nitrogen gas conduction and with a sample chamber temperature of 150 °C, for a maximum of 10 min. Luminescence images were obtained simultaneously with the CL measurements.

Results

CL was observed on light-exposed tablet surfaces. For each preparation, an increase in the CL value was observed with the duration of light exposure. In the same preparation with the same exposure time, CL tended to be higher in the order of Condition A < B < C. Moreover, CL increased even when no changes in color were observed by the naked eye. A comparison between preparations with the same main ingredients showed differences in the rate of increase in CL with exposure, and each was found to show a different reactivity to light.

Conclusions

To the best of our knowledge, this is the first study to visually capture the surface oxidation of tablets exposed to light using the CL method. The CL values, thought to be derived from photooxidation, increased with exposure of tablets and powders to light after SDP. This method can sensitively assess drug degradation due to photooxidation. Further research is needed to establish a CL method for assessing the stability of preparations in clinical settings.
Cultures as types and the utility of viable specimens for fungal nomenclature
Authors: Yurkov Andrey , Visagie Cobus M. , Crous Pedro W. , Hashimoto Akira , Baschien Christiane , Begerow Dominik , Kemler Martin , Schoutteten Nathan , Stadler Marc , Wijayawardene Nalin N. , Hyde Kevin D. , Zhang Ning , Boekhout Teun ,   ICTF Yeast Working Group, Yurkov Andrey , Boekhout Teun , Bai Feng-Yan , Begerow Dominik , Čadež Neža , Daniel Heide-Marie , Fell Jack W. , Groenewald Marizeth , Lachance Marc-André , Libkind Diego , Péter Gábor , Takashima Masako , Turchetti Benedetta , May Tom W. , Thines Marco , Hawksworth David L.
Published: July 2024

The debates over the requirement of the International Code of Nomenclature for algae, fungi, and plants (ICNafp) for a viable specimen to represent the name-bearing type material for a species or infraspecific taxon have a long history. Taxonomy of fungi commonly studied as living cultures exemplified by yeasts and moulds, strongly depend on viable reference material. The availability of viable cultures is also particularly useful for several groups of filamentous and dimorphic fungi. While the preservation of metabolically inactive cultures is permitted and recommended by the ICNafp, there is room for improvement. Below, we review the history and current status of cultures as the name-bearing type material under the Code. We also present a roadmap with tasks to be achieved in order to establish a stable nomenclatural system that properly manages taxa typified by viable specimens. Furthermore, we propose setting up rules and defining the nomenclatural status of ex-type cultures under Chapter F, the section of the ICNafp that includes provisions specific to names of fungi.
Utility of the 70-Gene MammaPrint Assay for Prediction of Benefit From Extended Letrozole Therapy in the NRG Oncology/NSABP B-42 Trial
Authors: Rastogi Priya , Bandos Hanna , Lucas Peter C. , van ‘t Veer Laura J. , Wei Jia-Perng J. , Geyer Charles E. , Fehrenbacher Louis , Chia Stephen K.L. , Brufsky Adam M. , Walshe Janice M. , Soori Gamini S. , Dakhil Shaker R. , Paik Soonmyung , Swain Sandra M. , Menicucci Andrea R. , Audeh M. William , Wolmark Norman , Mamounas Eleftherios P.
Published: July 2024

PURPOSE

MammaPrint (MP) determines distant metastatic risk and may improve patient selection for extended endocrine therapy (EET). This study examined MP in predicting extended letrozole therapy (ELT) benefit in patients with early-stage breast cancer (BC) from the NSABP B-42 trial.

PATIENTS AND METHODS

MP was tested in 1,866 patients randomly assigned to receive ELT or placebo. The primary end point was distant recurrence (DR). Secondary end points were disease-free survival (DFS) and BC-free interval (BCFI). Tumors were classified as MP high risk (MP-HR) or low risk (MP-LR). MP-LR tumors were further classified as ultralow risk (MP-UL) or low non-ultralow risk (MP-LNUL).

RESULTS

There was no statistically significant difference in ELT benefit on DR between MP-HR and MP-LR (interaction
P =
.38). MP-LR tumors (n = 1,160) exhibited a statistically significant 10-year benefit of 3.7% for DR (hazard ratio [HR], 0.43 [95% CI, 0.25 to 0.74];
P
= .002), whereas MP-HR tumors (n = 706) exhibited a nonsignificant 2.4% benefit (HR, 0.65 [95% CI, 0.34 to 1.24];
P
= .19). The 10-year ELT benefit was significant for DFS (7.8%) and BCFI (7.0%) for MP-LR tumors, whereas MP-HR tumors did not significantly benefit (interaction DFS:
P
= .015, BCFI:
P
= .006). In exploratory analysis, the 10-year ELT benefit was significant and more pronounced in MP-LNUL (n = 908) tumors: 4.0% for DR, 9.5% for DFS, and 7.9% for BCFI; the benefit in MP-UL (n = 252) tumors was not significant: 3% for DR, 1.8% for DFS, and 4.1% for BCFI.

CONCLUSION

The primary hypothesis of predictive ability of MP on DR was not confirmed. However, the secondary outcomes demonstrated MP was predictive of ELT response and identified a subset of patients with early-stage hormone receptor–positive BC (MP-LR) with improved outcomes from ELT. These data could have important clinical implications in patient selection beyond clinical risk assessment for EET.
Risk Without Reward: Differing Patterns of Chemotherapy Use Do Not Improve Outcomes in Stage II Early-Onset Colon Cancer
Authors: Leary Jacob B. , Hu Junxiao , Leal Alexis , Davis S. Lindsey , Kim Sunnie , Lentz Robert , Friedrich Tyler , Herter Whitney , Messersmith Wells A. , Lieu Christopher H.
Published: July 2024

PURPOSE

Rising rates of early-onset colon cancer (EOCC) present challenges in deciding how to optimally treat patients. Although standard of care for stage II CC is surgical resection, adding chemotherapy for high-risk disease, evidence suggests treatment selection may differ by age. We investigated whether adjuvant chemotherapy (AC) administration rates differ between patients with early- and later-onset stage II CC.

METHODS

Data originated from the nationwide Flatiron Health electronic health record (EHR)–derived deidentified database spanning January 1, 2003, to August 1, 2021. Adults with stage II CC were grouped as age 18-49 years (EOCC) and those age 50 years or older (later-onset colon cancer [LOCC]). Demographics, Eastern Cooperative Oncology Group score, tumor stage and site, and chemotherapy were included. Primary outcomes included rates of AC administration by age and ethnicity; secondary outcomes included overall survival (OS) and time to metastatic disease (TTMD). Univariate and multivariable logistic regression models evaluated relationships between chemotherapy administration, age, and ethnicity, adjusting for significant covariates.

RESULTS

One thousand sixty-five patients were included. Median age of patients with EOCC was 45.0 years versus 69.0 years for patients with LOCC. Adjusted multivariate analysis showed patients with EOCC received AC significantly more often than patients with LOCC. Non-Hispanic patients received AC at significantly lower rates than Hispanic patients in both cohorts. Subanalysis of stage IIA patients showed that patients with EOCC were more likely to receive AC than patients with LOCC. No significant differences in OS or TTMD were observed by age regardless of AC administration in stage II overall; however, patients with stage IIA EOCC receiving AC had significantly longer TTMD than those not receiving AC.

CONCLUSION

AC was given preferentially in stage II EOCC, even in stage IIA, despite deviation from guidelines. This may expose low-risk patients to unnecessary toxicities and suggests bias toward treating younger patients more aggressively, despite unclear evidence for better outcomes.
Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron
Authors: Ghanem Mohammed I. , Ashmawy Shimaa M. , El Maghraby Gamal M.
Published: July 2024

The aim was to employ site-dependent absorption of mirabegron (MB) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect.

Graphical Abstract