bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining the changes in metabolites of Dendrobium officinale juice fermented with starter cultures containing Saccharomycopsis fibuligera FBKL2.8DCJS1 and Lactobacillus paracasei FBKL1.3028 through untargeted metabolomics
Authors: Liu Wanlin , Luo Xiaoye , Qiu Shuyi , Huang Wu , Su Yanan , LI Linling
Published: March 2023

Background

The present study aimed to investigate the changes in volatile components and metabolites of Dendrobium officinale (D. officinale) juice fermented with starter cultures containing Saccharomycopsis fibuligera and Lactobacillus paracasei at 28 ℃ for 15 days and post-ripened at 4 ℃ for 30 days using untargeted metabolomics of liquid chromatography-mass spectrometry (LC–MS) and headspace solid-phase microextraction-gas chromatography (HS–SPME–GC–MS) before and after fermentation.

Results

The results showed that the alcohol contents in the S. fibuligera group before fermentation and after fermentation were 444.806 ± 10.310 μg/mL and 510.999 ± 38.431 μg/mL, respectively. Furthermore, the alcohol content in the fermentation broth group inoculated with the co-culture of L. paracasei + S. fibuligera was 504.758 ± 77.914 μg/mL, containing a significant amount of 3-Methyl-1-butanol, Linalool, Phenylethyl alcohol, and 2-Methyl-1-propanol. Moreover, the Ethyl L (-)-lactate content was higher in the co-culture of L. paracasei + S. fibuligera group (7.718 ± 6.668 μg/mL) than in the L. paracasei (2.798 ± 0.443 μg/mL) and S. fibuligera monoculture groups (0 μg/mL). The co-culture of L. paracasei + S. fibuligera significantly promoted the metabolic production of ethyl L (-)-lactate in D. officinale juice. The differential metabolites screened after fermentation mainly included alcohols, organic acids, amino acids, nucleic acids, and their derivatives. Twenty-three metabolites, including 11 types of acids, were significantly up-regulated in the ten key metabolic pathways of the co-culture group. Furthermore, the metabolic pathways, such as pentose and glucuronate interconversions, the biosynthesis of alkaloids derived from terpenoid and polyketide, and aminobenzoate degradation were significantly up-regulated in the co-culture group. These three metabolic pathways facilitate the synthesis of bioactive substances, such as terpenoids, polyketides, and phenols, and enrich the flavor composition of D. officinale juice.

Conclusions

These results demonstrate that the co-culture of L. paracasei + S. fibuligera can promote the flavor harmonization of fermented products. Therefore, this study provides a theoretical basis for analyzing the flavor of D. officinale juice and the functional investigation of fermentation metabolites.
Genome-wide characterization and expression analysis of MYB transcription factors in Chrysanthemum nankingense
Authors: Ai Penghui , Xue Jundong , Shi Zhongya , Liu Yuru , Li Zhongai , Li Tong , Zhao Wenqian , Khan Muhammad Ayoub , Kang Dongru , Wang Kangxiang , Wang Zicheng
Published: March 2023

Background

Chrysanthemum is a popular ornamental plant worldwide. MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factors play an important role in everything from stress resistance to plant growth and development. However, the MYB family of chrysanthemums has not been the subject of a detailed bioinformatics and expression investigation.

Results

In this study, we examined 324 CnMYB transcription factors from Chrysanthemum nankingense genome data, which contained 122 Cn1R-MYB, 183 CnR2R3-MYB, 12 Cn3R-MYB, 2 Cn4R-MYB, and 5 atypical CnMYB. The protein motifs and classification of CnMYB transcription factors were analyzed. Among them, motifs 1, 2, 3, and 4 were found to encode the MYB DNA-binding domain in R2R3-MYB proteins, while in other-MYB proteins, the motifs 1, 2, 3, 4, 5, 6, 7, and 8 encode the MYB DNA-binding domain. Among all CnMYBs, 44 genes were selected due to the presence of CpG islands, while methylation is detected in three genes, including CnMYB9, CnMYB152, and CnMYB219. We analyzed the expression levels of each CnMYB gene in ray floret, disc floret, flower bud, leaf, stem, and root tissues. Based on phylogenetic analysis and gene expression analysis, three genes appeared likely to control cellulose and lignin synthesis in stem tissue, and 16 genes appeared likely to regulate flowering time, anther, pollen development, and flower color. Fifty-one candidate genes that may be involved in stress response were identified through phylogenetic, stress-responseve motif of promoter, and qRT-PCR analyses. According to genes expression levels under stress conditions, six CnMYB genes (CnMYB9, CnMYB172, CnMYB186, CnMYB199, CnMYB219, and CnMYB152) were identified as key stress-responsive genes.

Conclusions

This research provides useful information for further functional analysis of the CnMYB gene family in chrysanthemums, as well as offers candidate genes for further study of cellulose and lignin synthesis, flowering traits, salt and drought stress mechanism.
Prehospital clinical practice guidelines for unintentional injuries: a scoping review and prioritisation process
Authors: Kuupiel Desmond , Jessani Nasreen S. , Boffa Jody , Naude Celeste , De Buck Emmy , Vandekerckhove Philippe , McCaul Michael
Published: March 2023

Background

Globally, millions of people die and many more develop disabilities resulting from injuries each year. Most people who die from injuries do so before they are transported to hospital. Thus, reliable, pragmatic, and evidence-based prehospital guidance for various injuries is essential. We systematically mapped and described prehospital clinical practice guidelines (CPGs) for injuries in the global context, as well as prioritised injury topics for guidance development and adolopment.

Methods

This study was sequentially conducted in three phases: a scoping review for CPGs (Phase I), identification and refinement of gaps in CPGs (Phase II), and ranking and prioritisation of gaps in CPGs (Phase III). For Phase I, we searched PubMed, SCOPUS, and Trip Database; guideline repositories and websites up to 23rdMay 2021. Two authors in duplicate independently screened titles and abstract, and full-text as well as extracted data of eligible CPGs. Guidelines had to meet 60% minimum methodological quality according to rigour of development domain in AGREE II. The second and third phases involved 17 participants from 9 African countries and 1 from Europe who participated in a virtual stakeholder engagement workshop held on 5 April 2022, and followed by an online ranking process.

Results

Fifty-eight CPGs were included out of 3,427 guidance documents obtained and screened. 39/58 (67%) were developed de novo compared to 19 that were developed using alternative approaches. Twenty-five out of 58 guidelines (43%) were developed by bodies in countries within the WHO European Region, while only one guideline was targeted to the African context. Twenty-five (43%) CPGs targeted emergency medical service providers, while 13 (22%) targeted first aid providers (laypeople). Forty-three CPGs (74%) targeted people of all ages. The 58 guidance documents contained 32 injury topics. Injuries linked to road traffic accidents such as traumatic brain injuries and chest injuries were among the top prioritised topics for future guideline development by the workshop participants.

Conclusion

This study highlights the availability, gaps and priority injury topics for future guideline development/adolopment, especially for the African context. Further research is needed to evaluate the recommendations in the 58 included CPGs for possible adaptation to the African context.
Perceived barriers and facilitators for adhering to COVID-19 preventive measures in Chile: a qualitative study in three large cities
Authors: Obach Alexandra , Cabieses Báltica , Vezzani Francisca , Robledo Consuelo , Blukacz Alice , Vial Pablo
Published: March 2023

Background

Globally, it has been reported that different social determinants of health -structural, sociodemographic, economic, living conditions and cultural factors- may affect opportunities to adhere to prevention measures against SARS-CoV-2. The objective of this study was to explore the perceptions around barriers and facilitators for adherence to COVID-19 prevention measures among the adult population residing in three large cities in Chile from a social determinants of health perspective.

Methods

Qualitative paradigm, multiple case-study design. Online semi-structured interviews were conducted with men and women aged 18 and over from different socioeconomic groups residing in three large cities. For participant recruitment and selection, purposive contacts were made based on community and social media networks, followed by snowball sampling. Saturation was reached at 61 participants, after which a thematic analysis was carried out with the support of AtlasTi software. The Ethics Committee of the Universidad del Desarrollo in Chile approved this study.

Results

The main perceived barriers to adherence to COVID-19 preventive measures are linked to structural social determinants of health such as income, occupation, gender, access to basic supplies, and housing. Perceived facilitators are the fear of contagion and the incorporation of measures into daily habits. The social communication of preventive measures by health authorities is perceived as punitive, affecting adherence once the fear of contagion decreased in the country. It is also perceived that the recommended preventive measures are disconnected from communities’ cultural practices and people´s identity, as well as affected by gender inequities and socioeconomic conditions that stakeholders in the country do not sufficiently address.

Conclusion

Study findings suggest that adherence to preventive measures, such as social distancing, mask use, and hand washing, could be promoted through their incorporation into the daily life habits of people and communities. These measures should consider the structural social determinants that generate multiple barriers to adherence, like poverty, occupational risks, and overcrowding. Socio-cultural dimensions of health and everyday risks need further understanding among the different communities in the country, allowing for differences in viewpoints and practices based on gender, age, place, and social identity.
Coping with loneliness and stigma associated with HIV in a resource-limited setting, making a case for mental health interventions; a sequential mixed methods study
Authors: Ninnoni Jerry Paul , Agyemang Sampson Opoku , Bennin Lydia , Agyare Elizabeth , Gyimah Leveana , Senya Kafui , Baddoo Nyonuku Akosua , Annor Francis , Obiri-Yeboah Dorcas
Published: March 2023

Background

Challenges such as stigma and loneliness may increase vulnerability to Human Immunodeficiency Virus (HIV) infection and negatively affect the quality of life of people living with HIV (PLHIV) despite the massive investment in access to antiretroviral therapy. This study aims to determine the level of loneliness and stigma and explore the coping resources employed by PLHIV in a resource-constrained setting.

Methods

This was a sequential mixed methods study conducted at the Cape Coast Teaching Hospital (CCTH) in Ghana between May and December 2021. A total of 395 adults were selected using a simple random sampling technique. HIV Stigma Scale and UCLA Loneliness Scale were used to collect quantitative data. A purposive sampling technique was applied to recruit 18 participants to saturation using a semi-structured interview guide. SPSS version 21 was used for the statistical analysis of the quantitative data. HIV-related loneliness and stigma levels were estimated, and bivariate and multivariable logistic regression were used to evaluate associated factors using a statistical significance of p-value (p < .05). In general, the thematic analysis approach by Braun and Clark was employed to analyse the qualitative data. Findings were then triangulated.

Results

The mean age was 46.79 years (± 12.53), 75.4% of the participants were female, with a prevalence of stigma of 99.0% (95%CI = 97.4–99.7) and loneliness of 30.1% (95%CI = 25.6–34.9). Tertiary-level education and instrumental support were associated with lower levels of loneliness. In contrast, comorbidity, personalised stigma, negative self-image, and self-blame were positively related to loneliness. Thematic analyses of the qualitative data produced a range of themes that showed that people living with HIV rely on personal resources, social support networks, and behaviour modification strategies to manage their condition. In particular, some of these strategies include; religiosity and spirituality, family and friends, medication and professional support systems.

Conclusion

The results suggest that PLHIV in the developing world face enormous challenges, socially, psychologically and financially. Although there have been global efforts to make HIV services accessible, the findings suggest a need for integrating mental health services contextually to reduce loneliness and HIV-related stigma to improve quality of life.
Increased D-dimer level was a poor predictor of neuroblastoma, especially in the high-risk group
Authors: Ma Yue , Li Changchun , Zhao Zhenzhen , Yang Chao , Zhou Jianwu , Peng Liang , Deng Xiaobin , Wang Shan
Published: March 2023

Purpose

D-dimer levels are associated with tumor progression and prognosis in various cancers. However, there are few research about the relationship between D-dimer and neuroblastoma (NB). This study assessed the relationships of D-dimer levels with clinical features and overall survival (OS) in patients with NB.

Methods

Information about the clinical features of 365 patients and the prognosis of 301 patients was collected. The relationship between D-dimer levels and clinical features or OS was analyzed. We constructed the risk score based on Cox regression analysis and verified the predictive efficacy of the model through ROC curve and calibration curve.

Results

The results showed that D-dimer levels were significantly increased in patients with nonmediastinal tumor, tumor larger than 10 cm, stage 3–4 disease, bone marrow metastasis, unfavorable histology, bone metastasis, NMYC amplification, and the high-risk group (all P < 0.05). The Kaplan–Meier survival analysis showed that there were significant differences in 3- and 5-year OS (87.4% vs. 32.3%, 79.3% vs. 32.3%, P < 0.0001) between the low D-dimer and high D-dimer groups. In the high-risk group, the OS of high D-dimer was significantly lower than that of low D-dimer (P < 0.0001). All cases were divided into the training cohort (N = 211) and the validation cohort (N = 90). Multivariate analysis further suggested that D-dimer level, bone metastasis, and NMYC status were independent prognostic factors for OS (all P < 0.05). Based on the above three factors, we constructed the risk score in the training cohort. Survival analysis showed that compared with the other groups, the group with 11 scores had the worst prognosis (3-year OS 0%, P < 0.0001). The time-dependent ROC analysis and calibration curve indicated that the risk score had good accuracy.

Conclusions

Patients with high D-dimer levels tended to have unfavorable clinical characteristics and poor prognosis.
The dimensional and morphological assessment of the frontal sinus in sex estimation among different populations
Authors: Zheng Bowen , Zhong Yuan , Al-Worafi Nassem Ali , Liu Yi
Published: March 2023

Background

The purpose of the present study was to determine the dimorphic potential of the frontal sinus (FS) index, area, and the combination of both variables to ascertain its accuracy in sex discrimination among Bosnian, Chinese, and Nepalese.

Methods

A retrospective study analyzed the digital standardized lateral cephalometric of 654 Bosnian, Chinese, and Nepalese adult patients (116 females, 102 males; age range 17–40 years). The following FS parameters were analyzed: The maximum height, width, and area of the FS, and the ratio of height and width was calculated as the FS index. The measurements were analyzed using logistic regression analysis for the FS index, area, and combined FS index and area.

Results

Statistically significant differences were observed between the mean values of the FS index and the area between females and males in each population. The highest frequency of bilateral absence of FS was detected among females, specifically in Chinese (6.6%). Logistic regression equation derived from the present study differentiated between sexes with higher classification percentages for the FS index and area with 62.4%, 75.2%, and 78.4% among Bosnian, Chinese, and Nepalese subjects, respectively.

Conclusions

The results of the present study highlight the implications of the combined FS index and area as a reliable approach in sex estimation in forensic science whenever both the FS structure and lateral cephalometric are available.
Research progress on non-protein-targeted drugs for cancer therapy
Authors: Zhang Yiwen , Lu Lu , Song Feifeng , Zou Xiaozhou , Liu Yujia , Zheng Xiaowei , Qian Jinjun , Gu Chunyan , Huang Ping , Yang Ye
Published: March 2023

Non-protein target drugs, especially RNA-based gene therapies for treating hereditary diseases, have been recognized worldwide. As cancer is an insurmountable challenge, no miracle drug is currently available. With the advancements in the field of biopharmaceuticals, research on cancer therapy has gradually focused on non-protein target-targeted drugs, especially RNA therapeutics, including oligonucleotide drugs and mRNA vaccines. This review mainly summarizes the clinical research progress in RNA therapeutics and highlights that appropriate target selection and optimized delivery vehicles are key factors in increasing the effectiveness of cancer treatment in vivo.
Effects of a remote-handling-concept–based task-oriented arm training (ReHab-TOAT) on arm-hand skill performance in chronic stroke: a study protocol for a two-armed randomized controlled trial
Authors: Elmanowski Jule , Seelen Henk , Geers Richard , Kleynen Melanie , Verbunt Jeanine
Published: March 2023

Background

Improving arm-hand skill performance is a major therapeutic target in stroke rehabilitation and needs intensive and varied training. However, guided treatment time is limited. Technology can assist in the training of patients, offering a higher intensity and more variety in content. A new task-oriented arm training approach was developed, using a ‘Remote Handling concept based’ device to provide haptic feedback during the performance of daily living activities (ReHab-TOAT). This study aims to investigate the effects of ReHab-TOAT on patients’ arm-hand function and arm-hand skill performance, quality of life of both patients in the chronic phase after stroke and their caregivers and the patients’ perception regarding the usability of the intervention.

Methods

A randomized clinical trial was designed. Adult chronic stroke patients suffering from hemiparesis and arm-hand problems, with an Utrechtse Arm-hand Test score of 1–3, will be invited to participate. Participants in the experimental group receive ReHab-TOAT additional to care as usual. ReHab-TOAT contains task-oriented arm training for stroke patients in combination with haptic feedback, generated by a remote handling device. They will train for 4 weeks, 3× per week, 1.5h per day. Participants in the control group will receive no additional therapy apart from care as usual. The Fugl-Meyer Assessment (FMA), measuring participants’ motor performance of the affected arm, is used as the primary outcome measure. Secondary outcome measures are arm-hand capacity of the patient (ARAT), perceived arm-hand skill performance (MAL), actual arm-hand skill performance (accelerometry), patients’ quality of life (EuoQol-5D) and caregivers’ quality of life (CarerQoL). Participants’ perception regarding the usability of the intervention, including both the developed approach and technology used, will be evaluated by the System Usability Scale and a questionnaire on the user experience of technology. Measurements will be performed at 1, 2, 3 and 4 weeks pre-intervention (baseline); immediately post-intervention; and 3, 6 and 9 months post-intervention. Statistical analysis includes linear mixed model analysis.

Discussion

This study is designed to investigate the evidence regarding the effects of ReHab-TOAT on patients’ performance at different levels of the International Classification of Functioning, disability and health (ICF) model, i.e. a framework measuring functioning and disability in relation to a health condition, and to provide insights on a successful development and research process regarding technology-assisted training in co-creation.

Trial registration

Netherlands Trial Register NL9541. Registered on June 22, 2021
The COSI trial: a study protocol for a multi-centre, randomised controlled trial to explore the clinical and cost-effectiveness of the Circle of Security-Parenting Intervention in community perinatal mental health services in England
Authors: Rosan Camilla , Dijk Kim Alyousefi-van , Darwin Zoe , Babalis Daphne , Cornelius Victoria , Phillips Rachel , Richards Lani , Wright Hannah , Pilling Steve , Fearon Pasco , Pizzo Elena , Fonagy Peter
Published: March 2023

Background

Perinatal mental health difficulties affect up to 27% of birthing parents during pregnancy and the first postnatal year, and if untreated are associated with difficulties in bonding and long-term adverse outcomes to children. There are large evidence gaps related to psychological treatment, particularly in group therapy approaches and parent-infant interventions. One intervention showing preliminary efficacious findings and user acceptability is Circle of Security-Parenting (COS-P), which is a brief, weekly, group programme. However, these studies were underpowered and predominantly non-randomised, and there has never been a research trial in England or with birthing parents experiencing severe and complex perinatal mental health difficulties. The aim of the research is to conduct a randomised control trial to test whether COS-P will reduce perinatal mental health symptoms in birthing parents accessing NHS perinatal mental health services, compared to treatment as usual (TAU). Secondary objectives include exploring whether the intervention improves parenting sensitivity, emotion regulation skills, attachment security and infant development. Additionally, the project aims to examine whether the intervention is acceptable to parents and NHS staff, and whether it is cost-effective.

Methods

COSI is an individually randomised, single-blind parallel arm controlled trial with an embedded internal pilot aiming to recruit 369 participants in a 2:1 ratio (intervention: TAU). Participants will be recruited from ten NHS community perinatal mental health services in England and screened based on clinical levels of both mental health symptoms (average CORE-OM score ≥ 1.1) and postnatal bonding difficulties (total PBQ score ≥ 12). This trial has 90% power to detect a MCID of 5 points on the CORE-OM. Primary and secondary outcomes will be measured at baseline, 3, 7 and 12 months after baseline. Service use and quality of life measures will also be collected alongside a process evaluation of parents’ and interveners’ views and experiences.

Discussion

This will be the first large pragmatic trial to test whether COS-P is effective for birthing parents with severe and complex perinatal mental health difficulties in improving their mental health symptoms. If shown to be effective, the intervention could be delivered widely across the NHS and other similar services globally.

Trial registration

ISRCTN, ISRCTN18308962. Registered 18 February 2022.
The need for a new keyword — “Trial registry-metaresearch” — to track certain uses of clinical trial registry records
Authors: Saberwal Gayatri
Published: March 2023

Public clinical trial registries contain a large amount of information about a large number of trials. Academic researchers have conducted various analyses using such data. However, some of these studies do not concern the medical condition or intervention that is the focus of each trial. We list examples of publications that have performed such analyses. Currently, there is no keyword to track relevant publications. Here, we propose a novel keyword, “Trial registry-metaresearch”, that could be used in such publications. This would be a great help to researchers who wish to more systematically search the literature for such metaresearch.
Umbilical catheter placement aided by coronary guidewires
Authors: Gendera Katarzyna , Georgiev Stanimir , Ewert Peter , Eckstein Stefan , Fusch Christoph , Rochow Niels
Published: March 2023

Catheterization of the umbilical vessels has proven to be an effective and relatively rapid method for gaining central vascular access in neonates. However, it can be technically difficult, the procedure may last 30 min or longer, and it can be associated with complications in some patients. We suggest using a coronary guidewire during catheterization of umbilical vessels to support the placement of umbilical catheters and significantly reduce a risk for complications. We tested the proposed technique in 6 successful ex vivo bench tests of catheterization of the umbilical vessels in stillborn piglets immediately after birth. We are confident that using coronary guidewire as a guiding tool during catheterization of the umbilical vessels is a rapid and safe method. We expect that it allows to obtain a vascular access with lower risk for dangerous procedural complications, which could be a lifesaving in critically ill patients. However, the approach needs to be validated in a comparative study in neonates.
COVID19 detection in appendix of acute appendicitis in a child: a case report and review of literature
Authors: Kono Jun , Yoshimaru Koichiro , Matsuura Toshiharu , Tamaki Akihiko , Takemoto Junkichi , Matsumoto Shinya , Hotta Taeko , Kohashi Kenichi , Oda Yoshinao , Tajiri Tatsuro
Published: March 2023

Background

Gastrointestinal symptoms are one of the most common presentations of Coronavirus disease-19 (COVID-19), even in children. Higher rates of complicated appendicitis have been demonstrated in the era of the COVID-19 outbreak, and it has been recently suggested that acute appendicitis may occur as a complication of COVID-19. However, the relationship between appendicitis and COVID-19 remains unclear.

Case presentation

A 7-year-old male presented to the pediatric emergency department with 2 days’ history of lower abdominal discomfort and tenderness. On examination, his abdomen was distended with diffuse mild tenderness at the lower abdomen, which was aggravated by movement. He was also tested and was found to be positive for SARS-CoV-2. Computed tomography showed perforated appendicitis with a fecalith. The patient was admitted and laparoscopic appendectomy was successfully performed. Postoperatively, a minor intra-abdominal abscess was present, which successfully treated with antibiotics. Histopathology showed a markedly inflamed appendix with mucosal ulceration and transmural neutrophilic inflammation, which was consistent with phlegmonous appendicitis. Reverse transcription quantitative polymerase chain reaction using a surgically extracted appendix specimen revealed the presence of SARS-CoV-2 virus, which indicated a pathophysiological relationship between appendicitis and COVID-19.

Conclusion

The present case will provide further understanding of pediatric patients with concomitant COVID-19 and acute appendicitis.
Vitamin D status, including serum levels and sun exposure are associated or correlated with bone mass measurements diagnosis, and bone density of the spine
Authors: khodabakhshi Adeleh , Davoodi Sayed Hossein , Vahid Farhad
Published: March 2023

Background

Osteoporosis is a health complication worldwide, especially in developing countries. The prevalence was reported to be 18.3% globally. While the effect of biochemical factors on fracture risk/odds has been documented, the association/correlation between serum 25(OH)D levels, vitamin D dietary intake, and sun exposure with bone mineral density (BMD) remains controversial. This study aimed to evaluate the association and correlation between vitamin D status, including serum levels, dietary intakes, and sun exposure with BMD. We hypothesized that vitamin D-related factors would have different correlations/associations with BMD, which would help better evaluate future studies’ results.

Methods

A total of 186 individuals were included in this study (winter 2020). BMD was measured by Dual-energy X-ray absorptiometry. Blood serum levels of 25(OH)D, phosphorus, calcium, parathyroid hormone (PTH), and calcitonin were tested using standard lab tests. Valid and reliable questionnaires were used for sun exposure assessment and dietary intakes.

Results

There was a significant protective association between spine BMD (classifications, two groups) (OR = 0.69, 95%CI: 0.50–0.94; p-value = 0.023), BMD diagnosis (classifications, two groups) (OR = 0. 69, 95%CI: 0.49–0.87; p-value = 0.036) and sun exposure. There was a significant and moderate correlation between Spine measurements (Spine BMD: Pearson correlation coefficient = 0.302, p-value = 0.046; Spine T-score: Pearson correlation coefficient = 0.322, p-value = 0.033, Spine Z-score: Pearson correlation coefficient = 0.328, p-value = 0.030) and serum 25(OH)D. In addition, participants with osteopenia and osteoporosis significantly consume a higher amount of soluble fiber than the normal BMD group. There was no significant correlation between vitamin D intake and BMD.

Conclusion

In conclusion, serum 25(OH)D levels and sun exposure are correlated and associated with BMD. However, prospective studies are needed to investigate the association between dietary vitamin D intake and BMD.
Effects of ambiguity on innovation strategies
Authors: Kim Hwa-Sung
Published: March 2023

Technological innovations significantly influence individual firms and other innovations, such as financial innovations. The future of a firm depends on its innovation investment strategy. According to the literature, innovation investments are affected by ambiguity. This study examines how ambiguity affects the innovation strategies of managers. We show that the innovation strategies of ambiguity-averse managers differ from those of ambiguity-neutral managers. Unlike ambiguity-neutral managers, ambiguity-averse managers consider a broader variety of innovation strategies for a wider range of future innovation arrival times. Regarding the profitability of a future innovation, ambiguity-averse managers delay the investment decision until the profitability of the innovation is less ambiguous. Moreover, we examine innovation strategies under various conditions, including the risk of innovation outdatedness, management disputes, and the varying volatility of innovations.
Adrenocortical carcinoma: Report of data from 66 patients with a rare disease at a cancer center.
Authors: Abduch Rafael Haikal dos Santos , Tariki Milena Shizue , Formiga Maria Nirvana , Bezerra Stephania Martins , Torrezan Giovana Tardin , Rinck José Augusto
Published: March 2023

1

Background: Adrenocortical carcinoma (ACC) is a rare (1,02 per million population) disease with unfavorable prognosis. In Brazil, the incidence is about 15 times higher than in the rest of the world, mainly due to significant prevalence of the TP53-R337H germline mutation in this population. Methods: We performed a retrospective analysis of 66 patients diagnosed with ACC at AC Camargo Cancer Center. Clinical, pathological, epidemiological, treatment and survival data were collected from the patient’s chart and described. Results: Between 2004 and 2021, 66 patients were diagnosed with ACC. The median age was 45 years and 56% were female. 23 (35%) patients had at least one first-degree relative with a history of cancer and 8 (12%) had a second primary tumor. Ten patients were tested for Li-Fraumeni Syndrome and 30% went positive (TP53- R337H germline mutation). Two of them had first-degree relative with cancer. In our cohort, 22 (33%) patients were stage IV, 14 (21%) stage III, 19 (29%) stage II, 6 (9%) stage I and 5 (7%) unknown stage. 36% of tumors were considered functional (cortisol and/or androgens). At 50 months the estimated OS was 25,9% in the metastatic group and 83% in the localized group (p<0.0001). Among localized patients, 13 (29%) received adjuvant mitotane and 31 (70%) were followed without mitotane. The 12-month DFS rate was 50,8% in the mitotane group versus 67,8% in the group without mitotane (p = 0.83). The Ki67 index was performed in 20 localized patients. The 12-month DFS rate was 58,2% in the high Ki67 index (>10%) group versus 75% in the low ki67 index (≤10%) group (p = 0.47). In metastatic scenario 31 (47%) underwent systemic treatment and the most common (71%) first line chemotherapy was EDP (etoposide-doxorubicin-cisplatin) plus mitotane with an objective response rate of 27% and 56% of them had progression of disease as the best response to treatment. 14 patients received second line and 7 received third line treatment. Gemcitabine-capecitabine,cisplatin-based and Pembrolizumab were the most common regimens used in advanced lines. Conclusions: ACC has a poor prognosis and a significant prevalence of personal and family history of cancer. EDP-mitotane was the preferred regimen used as the first line treatment. As a rare disease, worldwide data can add evidence for future improvements in adrenal cancer.
Germline genetic testing of patients with penile carcinoma.
Authors: Sonpavde Guru P. , Nielsen Sarah M. , Heald Brandie , Hatchell Kathryn E. , Esplin Edward D. , Nassar Amin
Published: March 2023

10

Background: Penile carcinoma (PeCa) is a rare malignancy with a mean age at diagnosis of 60 years. PeCa is epidemiologically associated with phimosis, HPV, HIV, tobacco, obesity, Psoralen and ultraviolet A photochemotherapy and lichen sclerosis. However, the prevalence and type of pathogenic germline variants (PGVs) associated with PeCa are unknown. Methods: A retrospective cohort of patients (pts) with PeCa who underwent germline testing (range of genes tested, 1-134) from 10/2016 to 5/2022 at a large commercial laboratory (Invitae) was evaluated. Clinician-reported clinical and demographic information from test requisition forms (TRF) were analyzed and the frequency and type of PGVs was determined. Pts were identified via keywords and/or ICD-10 codes for PeCa, but the final study cohort was limited to those whose diagnosis could be corroborated by details in the TRF and/or accompanying medical records. Pts with other pathologies were excluded. Results: Of the 29 pts who met inclusion criteria, the majority were White (65.5%), with a median age (range) of 62.5 years (36-79) at diagnosis. 44.8% of pts had documented squamous cell carcinoma (SCC) pathology, 55.2% of pts had an additional non-PeCa cancer, and 62.1% of pts had a documented family history of relevant cancers (penile, prostate, breast, ovarian, pancreatic and/or colorectal). Among 29 pts with PeCa, 3 harbored PGVs (10.3%) and 16 (55.2%) had > 1 variants of uncertain significance (VUS) in the absence of a PGV. Of the 3 positive pts, 2 harbored BRCA2 PGVs and one harbored a RAD51C PGV. One pt with a BRCA2 PGV had additional malignancies of the prostate and pancreas. Conclusions: This is the first study to our knowledge reporting PGVs in PeCa. PGVs in DNA repair genes ( BRCA2, RAD51C) were identified in 10.3% of selected high-risk PeCa pts with the majority exhibiting other malignancies or family history of malignancies. Larger cohorts of PeCa patients should be studied in pts with different ethnicities. Nonetheless, these data highlight the potential role of germline testing in selected PeCa pts as a tool to aid in clinical management, cascade testing and potential therapeutic relevance in the future.
Investigating documented reasons for withdrawal from clinical trials for patients with advanced prostate cancer (PCa).
Authors: Lloyd Jennifer , Nordblad Blake , Sahu Kamal Kant Kant , Swami Umang , Phunrab Tenzin Kunsang , Batten Julia Anne , Maxwell Lindsay , Kohli Manish , Gupta Sumati , Maughan Benjamin L. , Agarwal Neeraj
Published: March 2023

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Background: In clinical trials, treatment efficacy rates are based on participants who can tolerate treatment through study endpoints. Attrition from clinical trials can potentially lead to biased results (PMID: 30379822). Many oncology clinical trials censor the subject data of participants because of early trial intervention discontinuation due to adverse events (AEs), withdrawal of consent, or loss to follow-up. Despite high attrition rates reported across various oncology clinical trials (10-38%), there is inconsistency regarding investigating the reasons for withdrawal (PMID: 23132290). We aim to identify the causes of the withdrawal of participants with advanced PCa from clinical trials. Methods: In this IRB-approved single-center retrospective study (Sept 2014 to Sept 2022), the OnCore Research Database was used to capture data on the participants with advanced PCa enrolled in clinical trials. The included trials were specific to prostate cancer, and mixed solid tumor trials were excluded. Endpoint reports from all included trials were assessed. Participants who discontinued treatment for any reason were included. The primary objective was to obtain reasons for clinical trial withdrawal before primary endpoints, identify potential clinical intervention areas, and determine potential areas of adjustment to future study designs to improve retention rates. Eligibility criteria: diagnosis of metastatic prostate cancer, receipt of protocol treatment until discontinuation, and documentation of a reason for discontinuation of the protocol treatment. Results: 272 pts from the 18 clinical trials met eligibility criteria and were included in the study. The most common reasons documented for discontinuation were: the progression of disease (46.69%), other reasons (15.44%), adverse events (5.15%), personal preference (15.81%), and completion of protocol treatment (11.76%) of the total number of enrolled participants. We noted a statistically significant difference between participants who withdrew for other reasons in the castration-resistant versus castration-sensitive setting (6.08% vs. 32.38%, p value=0.03). Notably, declining performance status and symptom progression were listed under the “other reasons” category. The documentation of patient withdrawal due to clinical symptoms was reported across multiple withdrawal categories. Conclusions: In approximately one-third of participants, the reason for protocol treatment discontinuation was not apparent (documented as patient preference and other reasons with no further specifications). Further exploration of the exact reasons contributing to therapy discontinuation in these patients will be critical to improving patient retention in clinical trials.
Clinical outcomes of abiraterone acetate (AA) or enzalutamide (E) as first-line therapy (Rx) for men aged ≥75 with metastatic castration-resistant prostate cancer (mCRPC) according to previous use of docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC) in a multicenter international registry: A SPARTACUSS – Meet-URO 26 study.
Authors: Lee-Ying Richard M. , Saieva Calogero , Nuzzo Pier Vitale , Malgeri Andrea , Fotia Giuseppe , Zanardi Elisa , Rossetti Sabrina , Valenca Loana Bueno , Patrikidou Anna , Modesti Mikol , Martins Oliveira Thiago , Pignata Sandro , Fornarini Giuseppe , Procopio Giuseppe , Santini Daniele , Sweeney Christopher , Heng Daniel Yick Chin , De Giorgi Ugo , Russo Antonio , Francini Edoardo
Published: March 2023

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Background: The optimal management of mCRPC in men aged ≥75 is challenging, and there is a paucity of clinical data in the literature. Although AA and E are commonly used as 1st line Rx for mCRPC, it is unclear whether use of upfront D for mCSPC may impact their clinical efficacy or safety in this elderly population. Methods: Patients aged ≥75 who started AA or E as 1st line Rx for mCRPC within January 2015 - April 2019 were identified from the IRB approved databases of 10 institutions in Europe, South and North America. Demographic and clinicopathological data were collected from available medical records, including Gleason, prior local therapy, newly diagnosed metastatic disease, disease volume, ECOG, PSA and sites of metastases. Patients were classified by use of upfront D for mCSPC. The primary endpoints were overall survival (OS) from AA/E onset and OS from ADT start and safety of AA/E. The endpoints distributions including median (95% CI) were estimated by Kaplan-Meier method. Results: Of the 337 patients selected, 24 (7.1%) received ADT+D and 313 (92.9%) ADT alone for mCSPC. Patients with ADT+D tended to be younger (78 vs 81, p=0.022) and, albeit not statistically significant, had higher rates of Gleason score >8 (81.0% vs 62.6%, p=0.10), newly diagnosed (83.3% vs 65.6%, p=0.08) and high volume disease (45.8% vs 34.6%, p=0.28), compared to those with ADT alone. Median follow-up was 18.8 months. No significant difference of OS from ADT start or from AA/E onset was observed between the 2 cohorts (see table). Despite OS from ADT start being longer in those having ADT+D, OS from AA/E start was approximately 2 years in both cohorts. Rates of adverse events (AEs) of any grade (58.3% vs 52.1%, p=0.67) and grade ≥3 (12.5% vs 15.7%, p=1.0) did not significantly differ between the 2 cohorts. Conclusions: While limited by small sample size for ADT+D and retrospective study design, patients aged ≥75 having AA/E as 1st line mCRPC Rx showed similar survival outcomes and tolerability regardless of previous use of D for mCSPC. [Table: see text]
Disparities in germline testing by race/ethnicity and preferred language in patients with prostate cancer.
Authors: Thorn Annelise , Gordon Kelly , Tong Barry , Kwon Daniel H , Dhawan Mallika Sachdev , Borno Hala , Aggarwal Rahul Raj , Small Eric Jay , Blanco Amie
Published: March 2023

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Background: A remote Genetic Testing Station (GTS) workflow was implemented at an academic medical institution to expand access to genetic testing for patients with prostate cancer. During a telephone appointment, a genetic counselor assistant collects family history and facilitates genetics education, research consent, and remote sample collection for multi-gene panel testing. We compared testing completion and patient loss from workflow based on race/ethnicity and preferred language to identify disparities. Methods: Metrics were collected prospectively and analyzed retrospectively for patients with metastatic or high-grade prostate cancer referred to genetics between 3/15/2020 – 6/30/2022. Self-reported race, ethnicity, and preferred language were collected by chart review. Testing completion was compared between groups using Fisher’s exact test, with White non-Hispanic (WNH) and Preferred Language English (PLE) cohorts as controls. Odds ratios and 95% confidence intervals were reported. Patient loss at workflow checkpoints (scheduling, consenting, sample collection, and results release) was summarized for each group. Results: 827 eligible patients were identified: 78 (9%) Asian /Pacific Islander (API), 51 (6%) Black non-Hispanic (BNH), 42 (5%) Hispanic, and 625 (76%) WNH. 31 patients reporting other non-Hispanic race were not included in the analysis. 30 patients (4%) self-reported Preferred Language non-English (PLNE) and 797 (96%) PLE. BNH patients were significantly less likely to complete testing compared to WNH patients (OR 0.320, 95%CI: 0.168, 0.632, p<0.001). There was no difference in testing completion in API (OR 0.918, 95%CI: 0.467, 1.944, p=0.797) or Hispanic (OR 0.743, 95%CI: 0.325, 1.918, p=0.466) compared to WNH patients. PLNE were significantly less likely to complete testing (OR 0.393, 95%CI: 0.171, 0.965, p=0.016) compared to PLE patients. Patient loss occurred primarily at consenting and sample collection. 14% of BNH, and 9% of Hispanic patients did not consent, compared to 4% of WNH. 17% of PLNE did not consent compared to 5% of PLE patients. 13% of BNH did not return a sample, compared to 3% of WNH patients. Conclusions: In remote GTS, BNH and PLNE patients were significantly less likely to complete germline testing than WNH and PLE patients respectively. Disparities in patient loss were most pronounced at consenting and sample collection. Measures to mitigate disparities include assisted consenting (with interpreter as needed) and video-assisted or in-clinic sample collection. [Table: see text]
A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future.
Authors: Diaz Mejia Nely Mercy , Stecca Carlos , Jiang Di Maria , Fallah-Rad Nazanin , Bedard Philippe L. , Kumar Vikaash , Abdeljalil Osama , Zahralliyali Amer , Alqaisi Husam , Al-Ezzi Esmail Mutahar , Choy Vivian , Banwait Parmvir , Atenafu Eshetu , Sridhar Srikala S.
Published: March 2023

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Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Methods: We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Results: Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1*10*9/L vs 2.90*10*9/L, p<0.0001); and neutropenia rates were markedly lower (2% vs. 93%, P=<0.0001). Hospital admission rates were significantly lower in G-CSF users compared to non-users (19% vs. 69%, P<0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusions: During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.