bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide QTL and eQTL mapping reveal genes associated with growth rate trait of the Pacific white shrimp (Litopenaeus vannamei)
Authors: Chen Xiuli , Peng Min , Yang Chunling , Li Qiangyong , Feng Pengfei , Zhu Weilin , Zhang Yongde , Zeng Digang , Zhao Yongzhen
Published: April 2024

Background

Growth rate is a crucial economic trait for farmed animals, but the genetic regulation of this trait is largely unknown in non-model organisms such as shrimp.

Results

In this study, we performed genome-wide phenotypic quantitative trait loci (QTL) and expression quantitative trait loci (eQTL) mapping analyses to identify genes affecting the growth rate of Pacific white shrimp (Litopenaeus vannamei), which is the most commercially-farmed crustacean worldwide. We used RNA-sequencing of 268 individuals in a mapping population, and subsequently validated our findings through gene silencing and shrimp growth experiments. We constructed a high-density genetic linkage map comprising 5533 markers spanning 44 linkage groups, with a total distance of 6205.75 cM and an average marker interval of 1.12 cM. Our analyses identified 11 QTLs significantly correlated with growth rate, and 117,525 eQTLs. By integrating QTL and eQTL data, we identified a gene (metalloreductase STEAP4) highly associated with shrimp growth rate. RNA interference (RNAi) analysis and growth experiments confirmed that STEAP4 was significantly correlated with growth rate in L. vannamei.

Conclusions

Our results indicate that the comprehensive analysis of QTL and eQTL can effectively identify genes involved in complex animal traits. This is important for marker-assisted selection (MAS) of animals. Our work contributes to the development of shrimp breeding and available genetic resources.
Urogenital cultures and preterm birth in women with cervical cerclage: a single center retrospective cohort study
Authors: Seys Evelien , Page Ann-Sophie , Deprest Jan , Lannoo Lore , van Calsteren Kristel , Devlieger Roland , van der Merwe Johannes
Published: April 2024

Background

The leading hypothesis of the pathogenesis of cervical insufficiency suggests a role of cervical inflammation. Urogenital tract infections could play a causative role in this process. To test this hypothesis in women with a cervical cerclage, we aimed to retrospectively examine the relationship between gestational age (GA) at delivery and positive urogenital cultures.

Methods

This single center retrospective study reviewed the records of all women with a singleton pregnancy that underwent cervical cerclage (n = 203) between 2010 and 2020 at the University Hospital of Leuven, Belgium. Transvaginal cerclages were categorized as history indicated (TVC I, n = 94), ultrasound indicated (TVC II, n = 79) and clinically indicated (TVC III, n = 20). Additionally, ten women received transabdominal cerclage (TAC). Urogenital cultures (vaginal and urine) were taken before and after cerclage with 4-week intervals. Urogenital cultures were reported ‘positive’ if urine and/or vaginal cultures showed significant growth of a microorganism. Treatment decision depended on culture growth and clinical presentation. The primary aim was to evaluate the association between the urogenital culture results and the GA at delivery, for each of the cerclage groups. Secondarily, to investigate the effect of antibiotic treatment of positive cultures on GA at delivery.

Results

Positive pre-cerclage urogenital cultures were associated with lower GA at delivery in TVC III (positive culture 26w4d ± 40d vs. negative 29w6d ± 54d, p = 0.036). For TVC I, GA at delivery was longer when pre-cerclage urogenital cultures were positive (positive culture 38w0d ± 26d vs. negative 35w4d ± 42d, p = 0.035). Overall post-cerclage urogenital cultures status was not associated with a different GA at delivery. Treating patients with pre- or post-cerclage positive urogenital cultures did also not change GA at delivery.

Conclusion

Positive urogenital cultures taken before clinically indicated cerclage intervention may be associated with lower GA at delivery. However, there seems to be no benefit of antibiotic treatment or routine urogenital cultures during follow-up of asymptomatic women after cerclage placement.
Moderating effect of self-esteem between perfectionism and avoidant restrictive food intake disorder among Lebanese adults
Authors: Chaaya Roni , Hallit Rabih , Malaeb Diana , Sakr Fouad , Dabbous Mariam , El Khatib Sami , Fekih-Romdhane Feten , Hallit Souheil , Obeid Sahar
Published: April 2024

Background

Avoidant Restrictive Food Intake Disorder (ARFID) is a new diagnosis added to the DSM-5 characterized by pathological eating habits without body image disturbances. Previous findings demonstrated a general association between high levels of perfectionism and low levels of self-esteem in association with general eating disorders. However, research is scant when it comes to ARFID specifically. Subsequently, although self-esteem is seen to moderate the association between perfectionism and general eating disorders, this research study aims to explore the same moderation but with ARFID specifically.

Methods

For this study, 515 Lebanese adults from the general Lebanese population were recruited from all over Lebanon, 60.1% of which were females. The Arabic version of the Big Three Perfectionism Scale– Short Form (BTPS-SF) was used to measure self-critical, rigid and narcissistic perfectionism; the Avoidant/Restrictive Food Intake Disorder screen (NIAS) was used to score the ARFID variable; the Arabic-Single Item Self-Esteem (A-SISE) was the scale used to measure self-esteem.

Results

Across the different perfectionism types, self-esteem was seen to moderate the association between narcissistic perfectionism and ARFID (Beta = − 0.22; p =.006). At low (Beta = 0.77; p <.001), moderate (Beta = 0.56; p <.001) and high (Beta = 0.36; p =.001) levels of self-esteem, higher narcissistic perfectionism was significantly associated with higher ARFID scores.

Conclusion

This study brought to light some crucial clinical implications that highlight the need for interventions that help in the enhancement of self-esteem in patients with high perfectionism and ARFID. This study suggests that clinicians and healthcare professionals should focus more on risk factors influencing the development and maintenance of ARFID-like symptoms.
Risk factors for low back pain in the Chinese population: a systematic review and meta-analysis
Authors: Li Qiang , Peng Leyun , Wang Yiding , Yang Yonghui , Wang Zongbao
Published: April 2024

Background

In China, the world’s largest developing country, low back pain (LBP) is a common public health issue affecting workability. This meta-analysis aimed to systematically assess the risk factors of LBP in the Chinese population.

Methods

Four English language and four Chinese databases were searched, and cross-sectional studies on the risk factors for LBP in Chinese populations were identified and collected. The search timeframe covered the period from the establishment of the database to November 2023. Two researchers independently reviewed the literature, extracted the data, and evaluated the risk of bias. Begg’s and Egger’s tests were used to evaluate publication bias.

Results

Fifteen cross-sectional studies involving 86,575 people were included. Seven risk factors for LBP were identified. Six risk factors were statistically significant: Cigarette smoking (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.15, 2.08, P = 0.004, I2 = 72%), body mass index (BMI) ≥ 28 kg/m² (OR = 4.51; 95% CI: 3.36, 6.07, P < 0.00001, I2 = 8%), female sex (OR = 1.54; 95% CI: 1.25, 1.90, P < 0.0001, I2 = 63%), vibration exposure at work (OR = 1.65; 95% CI: 1.16, 2.34, P = 0.006, I2 = 84%), working overtime (OR = 2.57; 95% CI: 1.12, 5.91, P = 0.03, I2 = 85%), and lack of exercise (OR = 2.48; 95% CI: 1.62, 3.78, P < 0.0001, I2 = 0%). One risk factor that was not statistically significant was standing for long periods (OR = 1.02; 95% CI: 0.82, 1.26, P = 0.88, I2 = 73%).

Conclusions

This study found that smoking, a BMI ≥ 28 kg/m², female sex, vibration exposure at work, working overtime, and lack of exercise may be risk factors for LBP in the Chinese population. Because the included studies were cross-sectional and the certainty of the evidence was very low, the results need to be interpreted cautiously. Multicentre, high-quality studies should be conducted in the future. To reduce the prevalence of LBP, the Chinese government and hospitals must develop early screening programs and implement effective preventive and interventional measures.

Trial registration

This study is registered in the PROSPERO database (No. CRD42023447857).
Using propensity score matching analysis to compare between cardiometabolic risk factors and physical activity type in Korean adults: findings from a nationwide population-based survey
Authors: Kim Min-Hyo , Lee Ji-Won , Linton John A. , Lee Yaeji , Song Youhyun
Published: April 2024

Purpose

We aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population.

Methods

We categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM).

Results

The TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone.

Conclusion

TE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE.
The impact of quality-adjusted life years on evaluating COVID-19 mitigation strategies: lessons from age-specific vaccination roll-out and variants of concern in Belgium (2020-2022)
Authors: Willem Lander , Abrams Steven , Franco Nicolas , Coletti Pietro , Libin Pieter J. K. , Wambua James , Couvreur Simon , André Emmanuel , Wenseleers Tom , Mao Zhuxin , Torneri Andrea , Faes Christel , Beutels Philippe , Hens Niel
Published: April 2024

Background

When formulating and evaluating COVID-19 vaccination strategies, an emphasis has been placed on preventing severe disease that overburdens healthcare systems and leads to mortality. However, more conventional outcomes such as quality-adjusted life years (QALYs) and inequality indicators are warranted as additional information for policymakers.

Methods

We adopted a mathematical transmission model to describe the infectious disease dynamics of SARS-COV-2, including disease mortality and morbidity, and to evaluate (non)pharmaceutical interventions. Therefore, we considered temporal immunity levels, together with the distinct transmissibility of variants of concern (VOCs) and their corresponding vaccine effectiveness. We included both general and age-specific characteristics related to SARS-CoV-2 vaccination. Our scenario study is informed by data from Belgium, focusing on the period from August 2021 until February 2022, when vaccination for children aged 5-11 years was initially not yet licensed and first booster doses were administered to adults. More specifically, we investigated the potential impact of an earlier vaccination programme for children and increased or reduced historical adult booster dose uptake.

Results

Through simulations, we demonstrate that increasing vaccine uptake in children aged 5-11 years in August–September 2021 could have led to reduced disease incidence and ICU occupancy, which was an essential indicator for implementing non-pharmaceutical interventions and maintaining healthcare system functionality. However, an enhanced booster dose regimen for adults from November 2021 onward could have resulted in more substantial cumulative QALY gains, particularly through the prevention of elevated levels of infection and disease incidence associated with the emergence of Omicron VOC. In both scenarios, the need for non-pharmaceutical interventions could have decreased, potentially boosting economic activity and mental well-being.

Conclusions

When calculating the impact of measures to mitigate disease spread in terms of life years lost due to COVID-19 mortality, we highlight the impact of COVID-19 on the health-related quality of life of survivors. Our study underscores that disease-related morbidity could constitute a significant part of the overall health burden. Our quantitative findings depend on the specific setup of the interventions under review, which is open to debate or should be contextualised within future situations.
Dimensional stability of 3D-printed edentulous and fully dentate hollowed maxillary models over periods of time
Authors: Zarbah Mohammad , Aldowah Omir , Alqahtani Nasser M. , Alqahtani Saud Ali , Alamri Maha , Alshahrani Reem , Mohsinah Noaf
Published: April 2024

Background

Dental casts made utilising digital workflow are becoming more common because to their speed and cost savings. However, studies on their dimensional accuracy over time with diverse designs are missing.

Objective

The aim of this in vitro study was to assess the dimensional stability of 3D-printed edentulous and fully dentate hollowed maxillary models with 50-micrometer resolution over 1 day, 14 days, and 28 days using surface matching software.

Methods

Scanned edentulous and fully dentate maxillary typodont models were used as references. The models were scanned by a desktop lab scanner of 15-micrometer accuracy (D900, 3Shape). Then, the files were used in designing software (Meshmixer, Autodesk) to create hollowed maxillary casts. Fifteen edentulous and 15 fully dentate (total of 30) models were printed using a DLP lab printer (Cara print 4.0, Kulzer). The 3D-printed models were scanned using the same desktop lab scanner of 15-micrometer accuracy at intervals of baseline days, 1 day, 14 days, and 28 days to assess the effect of aging (n = 120). The dimensional changes were quantified and compared using the root mean square (RMS) method, expressed in micrometres (µm). The study employed repeated measures analysis of variance (ANOVA) to assess and compare the root mean square (RMS) values across the variables. The data was analysed using SPSS (26, Chicago, Illinois, USA).

Results

The RMS of the edentulous models rapidly increased from a mean value of 0.257 at the beginning of the study to 0.384 after twenty-eight days. However, the mean RMS values for the dentate models did not change much over the four intervals. It varied only from 0.355 to 0.347. The mean values for edentulous patients increased from 0.014 to 0.029 during the period from baseline to twenty-eight days. However, the mean average values decreased for the dentate models from 0.033 to 0.014 during this period. By utilizing ANOVA, mean RMS values increased insignificantly till one day but significantly to fourteen and twenty-eight days. Dentate model mean values differed insignificantly across four intervals. Repeated measures ANOVA for combined and separated data showed no significant differences across edentulous, dentate, and total models over times.

Conclusion

The study revealed changes in the dimensions of 3D-printed edentulous models over a span of 3 and 4 weeks. Caution should be applied when using 3D-printed dental master models for constructing definitive prostheses on edentulous models over a period of 3 to 4 weeks.
Development and validation of impact of early integration of palliative care and oncology(IEI PCO) questionnaire: a survey for medical oncologists and nurses
Authors: Abdullah Abdulrahman Abdulaziz , Abd-El-Gawad Wafaa Mostafa , AboSerea Sobhi Mostafa , Ali Fatma AbdelShakor , Ali Saima
Published: April 2024

Objectives

Many associations have recently recommended early integration of oncology and palliative care for more standard cancer care and better quality of life. We aimed to create a questionnaire to assess the opinion of medical oncologists and nurses about the clinical impact of the integrated palliative care and oncology (PCO) program.

Methods

A novel semi-structured questionnaire called Impact of Early Integration of Palliative Care Oncology (IEI PCO) questionnaire was developed and tested for validity and reliability then distributed to the oncologists and nurses working in Kuwait Cancer Control Center.

Results

After the pilot stage, testing the final questionnaire for validity and reliability was done with satisfactory results. Finally, the complete questionnaires were 170 out of 256 (response rate 66.41%). More awareness about the available palliative care services and the new available PCO services (p-value < 0.001 for all). Most of the oncologists and nurses agreed with the currently available structure of PCO, appreciated the patients’ discharge plan and continuity of care of palliative medicine, admitted less work burden, a better attitude, and higher satisfaction (p-value for all < 0.001) toward palliative care. Significant improvements in symptoms were appreciated by oncologists and nurses after the integration of palliative care (p-value for all < 0.001. Oncologists and nurses valued repeated honest communication, discussion of the goals of care, dealing more effectively with ending active treatment, and higher acceptance of patients and families of PC policy of transfer, and significant progress in the care of end-of-life symptoms (p-value for all < 0.001).

Conclusions

The IEI PCO questionnaire demonstrated the psychometric criteria for content, face, and construct validity and reliability. It provides a valuable tool to assess the impact of PCO integration. The opinion of medical oncologists and nurses was significantly positive toward the early integration of PCO in Kuwait in most aspects of care. This integration led to improved symptom control, end-of-life care, communication, and planned discharge and follow-up plans. Moreover, decreases the work burden, improves attitude, higher satisfaction of the oncology staff, and continuity of care.
Interprofessional socialization of first-year medical and midwifery students: effects of an ultra-brief anatomy training
Authors: Bostedt Dana , Dogan Ebrar Hümeyra , Benker Sina Chole , Rasmus Maret Antje , Eisner Emily , Simon Nadine Lana , Schmitz Martina , Missler Markus , Darici Dogus
Published: April 2024

Background

Interprofessionalism is considered a key component in modern health profession education. Nevertheless, there remains ongoing debate about when and where to introduce interprofessional trainings in the curriculum. We identified anatomy, a subject commonly shared among health professionals, as a practical choice for initiating early intergroup-contact between first-year medical and midwifery students. Our study examined the effects of a four-hour block course in anatomy on interprofessional socialization and valuing, as well as long-term effects on intergroup contact.

Methods

Based on different concepts and theories of learning, we implemented 12 interprofessional learning stations. Several measures were taken to foster group cohesion: (1) self-directed working in interprofessional tandems on authentic obstetric tasks, (2) competing with other tandems, (3) creating positive interdependencies during task completion, and (4) allowing room for networking. In a pre-post design with a three-month follow-up, we assessed the outcomes of this ultra-brief training with qualitative essays and quantitative scales.

Results

After training, both groups improved in interprofessionalism scores with strong effect sizes, mean difference in ISVS-21 = 0.303 [95% CI: 0.120, 0.487], P < .001, η² = 0.171, while the scales measuring uniprofessional identity were unaffected, mean difference in MCPIS = 0.033 [95% CI: -0.236, 0.249], P = .789. A follow-up indicated that these positive short-term effects on the ISVS-21 scale diminished after 12 weeks to baseline levels, yet, positive intergroup contact was still reported. The qualitative findings revealed that, at this initial stage of their professional identity development, both medical and midwifery students considered interprofessionalism, teamwork and social competencies to be of importance for their future careers.

Conclusion

This study advocates for an early implementation of interprofessional learning objectives in anatomical curricula. Young health profession students are receptive to interprofessional collaboration at this initial stage of their professional identity and derive strong advantages from a concise training approach. Yet, maintaining these gains over time may require ongoing support and reinforcement, such as through longitudinal curricula. We believe that an interprofessional socialization at an early stage can help break down barriers, and help to avoid conflicts that may arise during traditional monoprofessional curricula.
Exploring a revised interprofessional learning curriculum in undergraduate health education programs at Linköping University
Authors: Karlsson Elin A. , Kvarnström Susanne , Kvarnström Maria
Published: April 2024

Background

Interprofessional education aiming at providing competencies require evaluation in order to ensure that outcomes match the needs and ambitions. Health professionals today need a broad range of skills and competencies in order to provide high quality care, including interprofessional competence. Linköping University has been a pioneer in interprofessional learning for decades and this study provides one example of how a curriculum revision can be carried out. The aim of this study was to study the intentions and outcomes of a revised interprofessional learning curriculum in health professions education programs.

Methods

This was a qualitative study, including documents (n = 143) and complementary interviews with key individuals (n = 4). Data included syllabuses, study guides, educational program plans, supervisor guides, and interview transcripts. A qualitative document analysis and a content analysis with a directed approach was used, applying a theoretical framework for curriculum development that guided the analysis.

Results

The analysis resulted in one overarching theme named “A planned, lived, and attended curriculum” including four main categories inspired by a theoretical framework. The findings demonstrate a variety of aspects relating to the why and how of curriculum revision. The introduction of a programme director in interprofessional learning, with a mandate equal to respective program directors, seemed to contribute to legitimacy. Further, the partnership between the university and the healthcare sector had an impact on the curriculum revision, in that healthcare had a say in the revision regarding what suggestions to implement or not. The expectations of the teachers involved were high, although clear support structures seemed to be lacking.

Conclusions

This study has identified some of the important links between teachers, organizational prerequisites, and healthcare when revising an existing fully integrated curriculum in interprofessional learning for health professions education programs. The aim of this curriculum revision was to legitimize and provide education that is up to date with current healthcare needs and to provide students with competencies to collaborate in teams to ensure patient safety. When redesigning a curriculum there seems to be a fine balance between pedagogical innovation and pragmatism. This study identified that the links provided between organizational support structures and the expectations on teachers were not aligned.
From algorithms to action: improving patient care requires causality
Authors: van Amsterdam Wouter A. C. , de Jong Pim A. , Verhoeff Joost J. C. , Leiner Tim , Ranganath Rajesh
Published: April 2024

In cancer research there is much interest in building and validating outcome prediction models to support treatment decisions. However, because most outcome prediction models are developed and validated without regard to the causal aspects of treatment decision making, many published outcome prediction models may cause harm when used for decision making, despite being found accurate in validation studies. Guidelines on prediction model validation and the checklist for risk model endorsement by the American Joint Committee on Cancer do not protect against prediction models that are accurate during development and validation but harmful when used for decision making. We explain why this is the case and how to build and validate models that are useful for decision making.
Nurses’ experiences of the attributes of the organizational citizenship behavior: a qualitative content analysis
Authors: Khajoei Rahimeh , Jokar Mozhgan , Vasli Parvaneh
Published: April 2024

Background and aim

Organizational citizenship behavior (OCB) among nurses, as the key human resources in healthcare systems, is of paramount importance to nursing care quality and patient outcomes. The present study was to reflect on Iranian nurses’ experiences of OCB.

Methods

This qualitative study was completed in Iran from December 2022 to October 2023. In total, 20 nurses involved in hospitals, meeting the inclusion criteria, were recruited by purposive sampling with maximum variation. The data were then collected using 20 semi-structured interviews, each one lasting 30–60 min, and finally analyzed through qualitative content analysis.

Results

The data analysis revealed the nurses’ experiences of OCB under nine subcategories and three main categories, including (i) “helping behavior”, comprised of four subcategories of helping colleagues at work, helping colleagues outside of work, boosting morale, and creating a culture of support and appreciation, (ii) “extra-role behavior” with two subcategories of cooperation in advancing tasks, and creativity and efforts to promote services, and (iii) “contribution to professional growth and development”, consisting of two subcategories of individual professional development and support for colleagues’ professional development.

Conclusion

Nursing managers and instructors can use the study results to enhance nurses’ OCB by evaluating and employing nurses, and incorporating OCB into nursing curricula and continuous training programs.
Carbon dots as a novel photosensitizer for photodynamic therapy of cancer and bacterial infectious diseases: recent advances
Authors: Sun Lingxiang , Zhao Yifan , Peng Hongyi , Zhou Jian , Zhang Qingmei , Yan Jingyu , Liu Yingyu , Guo Susu , Wu Xiuping , Li Bing
Published: April 2024

Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.

Graphical Abstract
Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study
Authors: Kim Juwan , Hong Seung Soo , Kim Sung Hyun , Hwang Ho Kyong , Kang Chang Moo
Published: April 2024

Background

Pancreatic neuroendocrine tumors (PNETs) represent 1–2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched.

Methods

This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test.

Results

Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence.

Conclusion

This study’s findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious “wait-and-see” approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.
Targeting Wnt/β-catenin signaling and its interplay with TGF-β and Notch signaling pathways for the treatment of chronic wounds
Authors: Gumede Dimakatso B. , Abrahamse Heidi , Houreld Nicolette N.
Published: April 2024

Wound healing is a tightly regulated process that ensures tissue repair and normal function following injury. It is modulated by activation of pathways such as the transforming growth factor-beta (TGF-β), Notch, and Wnt/β-catenin signaling pathways. Dysregulation of this process causes poor wound healing, which leads to tissue fibrosis and ulcerative wounds. The Wnt/β-catenin pathway is involved in all phases of wound healing, primarily in the proliferative phase for formation of granulation tissue. This review focuses on the role of the Wnt/β-catenin signaling pathway in wound healing, and its transcriptional regulation of target genes. The crosstalk between Wnt/β-catenin, Notch, and the TGF-β signaling pathways, as well as the deregulation of Wnt/β-catenin signaling in chronic wounds are also considered, with a special focus on diabetic ulcers. Lastly, we discuss current and prospective therapies for chronic wounds, with a primary focus on strategies that target the Wnt/β-catenin signaling pathway such as photobiomodulation for healing diabetic ulcers.
Using functional principal component analysis (FPCA) to quantify sitting patterns derived from wearable sensors
Authors: Zablocki Rong W. , Hartman Sheri J. , Di Chongzhi , Zou Jingjing , Carlson Jordan A. , Hibbing Paul R. , Rosenberg Dori E. , Greenwood-Hickman Mikael Anne , Dillon Lindsay , LaCroix Andrea Z. , Natarajan Loki
Published: April 2024

Background

Sedentary behavior (SB) is a recognized risk factor for many chronic diseases. ActiGraph and activPAL are two commonly used wearable accelerometers in SB research. The former measures body movement and the latter measures body posture. The goal of the current study is to quantify the pattern and variation of movement (by ActiGraph activity counts) during activPAL-identified sitting events, and examine associations between patterns and health-related outcomes, such as systolic and diastolic blood pressure (SBP and DBP).

Methods

The current study included 314 overweight postmenopausal women, who were instructed to wear an activPAL (at thigh) and ActiGraph (at waist) simultaneously for 24 hours a day for a week under free-living conditions. ActiGraph and activPAL data were processed to obtain minute-level time-series outputs. Multilevel functional principal component analysis (MFPCA) was applied to minute-level ActiGraph activity counts within activPAL-identified sitting bouts to investigate variation in movement while sitting across subjects and days. The multilevel approach accounted for the nesting of days within subjects.

Results

At least 90% of the overall variation of activity counts was explained by two subject-level principal components (PC) and six day-level PCs, hence dramatically reducing the dimensions from the original minute-level scale. The first subject-level PC captured patterns of fluctuation in movement during sitting, whereas the second subject-level PC delineated variation in movement during different lengths of sitting bouts: shorter (< 30 minutes), medium (30 -39 minutes) or longer (> 39 minute). The first subject-level PC scores showed positive association with DBP (standardized $$\hat{\beta }$$

β
^

: 2.041, standard error: 0.607, adjusted p = 0.007), which implied that lower activity counts (during sitting) were associated with higher DBP.

Conclusion

In this work we implemented MFPCA to identify variation in movement patterns during sitting bouts, and showed that these patterns were associated with cardiovascular health. Unlike existing methods, MFPCA does not require pre-specified cut-points to define activity intensity, and thus offers a novel powerful statistical tool to elucidate variation in SB patterns and health.

Trial registration

ClinicalTrials.gov NCT03473145; Registered 22 March 2018; https://clinicaltrials.gov/ct2/show/NCT03473145; International Registered Report Identifier (IRRID): DERR1-10.2196/28684
Vpr driving DNA methylation variation of CD4 + T cells in HIV-1 infection
Authors: Wang Peipei , Meng Zhuoyue , Deng Kai , Gao Zhiliang , Cai Jinfeng
Published: April 2024

Background

Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted.

Methods

In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection.

Results

We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes.

Conclusions

These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.
Quality of occlusal outcome in adult class II patients after maxillary total arch distalization with interradicular mini-screws
Authors: Janssens Yann , Foley Patrick F. , Beyling Frauke , Schwestka-Polly Rainer , Schmid Jonas Q.
Published: April 2024

Background

The aim of the investigation was to evaluate if a Class II malocclusion in adult patients can be successfully corrected by maxillary total arch distalization with interradicular mini-screws in combination with completely customized lingual appliances (CCLA).

Methods

Two patient groups were matched for age and gender to determine differences in the quality of final treatment outcome. The treatment results of 40 adult patients with a Class I malocclusion (Group 1) were compared with those of 40 adult patients with a moderate to severe Class II malocclusion (Group 2). All patients had completed treatment with a CCLA (WIN, DW Lingual Systems, Bad Essen, Germany) without overcorrection in the individual treatment plan defined by a target set-up. To compare the treatment results of the two groups, 7 measurements using the American Board of Orthodontics Model Grading System (ABO MGS) and linear measurements for anterior-posterior (AP) and vertical dimensions were assessed at the start of lingual treatment (T1), after debonding (T2B), and compared to the individual target set-up (T2A).

Results

A statistically significant AP correction (mean 4.5 mm, min/max 2.1/8.6, SD 1.09) was achieved in Group 2, representing 99% of the planned amount. The planned overbite correction was fully achieved in both the Class I and Class II groups. There was a statistically significant improvement in the ABO scores in both groups (Group 1: 39.4 to 17.7, Group 2: 55.8 to 17.1), with no significant difference between the two groups at T2B. 95% of the adult patients in Group 1 and 95% in Group 2 would meet the ABO standards after maxillary total arch distalization with a CCLA and interradicular mini-screws.

Conclusions

CCLAs in combination with interradicular mini-screws for maxillary total arch distalization can successfully correct moderate to severe Class II malocclusions in adult patients. The quality of the final occlusal outcome is high and the amount of the sagittal correction can be predicted by the individual target set-up.
Researchers should no longer delay implementation of Pap screening in low and middle income countries pending research into novel screening approaches
Authors: Suba Eric J
Published: April 2024

A study coordinated by Groesbeck Parham and Mark Schiffman describes a novel approach to single-visit, point-of-care cervical screening and triage for low and middle income countries (LMICs) that uses an HPV screening test that is not affordable in LMICs combined with a triage test that is not available at the point of care. Pap smears are feasible, affordable, and well-suited for single-visit, point-of-care cervical screening and triage in LMICs. Research into a discredited cervical screening test, funded by the US National Cancer Institute, contributed to at least 500,000 preventable cervical cancer deaths by delaying implementation of Pap screening throughout India for 18 years. Researchers should no longer delay implementation of Pap screening in LMICs pending research into novel screening approaches. Instead, researchers should prioritize cervical screening approaches that will save as many lives as quickly as possible in LMICs. To that end, Parham et al. should implement good-quality, single-visit, point-of-care Pap smear screening in LMICs until better-quality, single-visit, point-of-care HPV screening becomes widely affordable in LMICs.
hadge: a comprehensive pipeline for donor deconvolution in single-cell studies
Authors: Curion Fabiola , Wu Xichen , Heumos Lukas , André Mylene Mariana Gonzales , Halle Lennard , Ozols Matiss , Grant-Peters Melissa , Rich-Griffin Charlotte , Yeung Hing-Yuen , Dendrou Calliope A. , Schiller Herbert B. , Theis Fabian J.
Published: April 2024

Single-cell multiplexing techniques (cell hashing and genetic multiplexing) combine multiple samples, optimizing sample processing and reducing costs. Cell hashing conjugates antibody-tags or chemical-oligonucleotides to cell membranes, while genetic multiplexing allows to mix genetically diverse samples and relies on aggregation of RNA reads at known genomic coordinates. We develop hadge (hashing deconvolution combined with genotype information), a Nextflow pipeline that combines 12 methods to perform both hashing- and genotype-based deconvolution. We propose a joint deconvolution strategy combining best-performing methods and demonstrate how this approach leads to the recovery of previously discarded cells in a nuclei hashing of fresh-frozen brain tissue.
Clustering of predicted loss-of-function variants in genes linked with monogenic disease can explain incomplete penetrance
Authors: Beaumont Robin N. , Hawkes Gareth , Gunning Adam C. , Wright Caroline F.
Published: April 2024

Background

Genetic variants that severely alter protein products (e.g. nonsense, frameshift) are often associated with disease. For some genes, these predicted loss-of-function variants (pLoFs) are observed throughout the gene, whilst in others, they occur only at specific locations. We hypothesised that, for genes linked with monogenic diseases that display incomplete penetrance, pLoF variants present in apparently unaffected individuals may be limited to regions where pLoFs are tolerated. To test this, we investigated whether pLoF location could explain instances of incomplete penetrance of variants expected to be pathogenic for Mendelian conditions.

Methods

We used exome sequence data in 454,773 individuals in the UK Biobank (UKB) to investigate the locations of pLoFs in a population cohort. We counted numbers of unique pLoF, missense, and synonymous variants in UKB in each quintile of the coding sequence (CDS) of all protein-coding genes and clustered the variants using Gaussian mixture models. We limited the analyses to genes with ≥ 5 variants of each type (16,473 genes). We compared the locations of pLoFs in UKB with all theoretically possible pLoFs in a transcript, and pathogenic pLoFs from ClinVar, and performed simulations to estimate the false-positive rate of non-uniformly distributed variants.

Results

For most genes, all variant classes fell into clusters representing broadly uniform variant distributions, but genes in which haploinsufficiency causes developmental disorders were less likely to have uniform pLoF distribution than other genes (P < 2.2 × 10−6). We identified a number of genes, including ARID1B and GATA6, where pLoF variants in the first quarter of the CDS were rescued by the presence of an alternative translation start site and should not be reported as pathogenic. For other genes, such as ODC1, pLoFs were located approximately uniformly across the gene, but pathogenic pLoFs were clustered only at the end, consistent with a gain-of-function disease mechanism.

Conclusions

Our results suggest the potential benefits of localised constraint metrics and that the location of pLoF variants should be considered when interpreting variants.
An unusual case of severe asphyxia with the fetal position unexpectedly inverted in a malformed uterus: a case report
Authors: Abe Jiro , Nasu Takashi , Noro Ayumu , Tsubaki Junko
Published: April 2024

Background

We present a severe neonatal consequence due to the unexpected and crucial inversion of the fetal position after sudden termination of tocolysis during early labor of a woman with congenital uterine anomaly. It has been reported that congenital uterine anomalies latently affect the fetal position. The clinical pitfalls in childbirth with uterine anomalies are discussed here on the basis of clinical evidence.

Case presentation

At a perinatal medical center in Japan, a 29-year-old Japanese mother who had a history of bicornuate uterus, received tocolysis to prolong her pregnancy for 5 days during the late preterm period after preterm-premature rupture of the membrane. She gave birth to a 2304 g male neonate of the gestational age of 35 weeks and 5 days with severe asphyxia by means of crash cesarean section for fetal sustained bradycardia after sudden termination of tocolysis. We found the fetal position to reverse from cephalic to breech position during early labor. He ended up having severe cerebral palsy after brain cooling against hypoxic-ischemic encephalopathy for 3 days. The mechanism of inversion from cephalic to breech position without amnionic fluid remains unclear, although women with a known diagnosis of a uterine anomaly have higher risk of adverse outcomes such as malpresentation.

Conclusions

When considering the clinical course of this case on the basis of the medical reports, we suspected that uterine anomalies and changes in intrauterine pressure could cause fetal malpresentation and adverse neonatal outcomes.
Biodistribution and radiation dosimetry of [99mTc]Tc-N4-BTG in patients with biochemical recurrence of prostate cancer
Authors: Rinscheid Andreas , Gäble Alexander , Wienand Georgine , Dierks Alexander , Kircher Malte , Günther Thomas , Patt Marianne , Bundschuh Ralph A. , Lapa Constantin , Pfob Christian H.
Published: April 2024

Background

In patients with prostate cancer (PCa), imaging with gastrin-releasing peptide receptor (GRPR) ligands is an alternative to PSMA-targeted tracers, particularly if PSMA expression is low or absent. [99mTc]Tc-N4-BTG is a newly developed GRPR-directed probe for conventional scintigraphy and single photon emission computed tomography (SPECT) imaging. The current study aims to investigate the safety, biodistribution and dosimetry of [99mTc]Tc-N4-BTG in patients with biochemical recurrence (BCR) of PCa.

Results

No adverse pharmacologic effects were observed. Injection of [99mTc]Tc-N4-BTG resulted in an effective dose of 0.0027 ± 0.0002 mSv/MBq. The urinary bladder was the critical organ with the highest mean absorbed dose of 0.028 ± 0.001 mGy/MBq, followed by the pancreas with 0.0043 ± 0.0015 mGy/MBq, osteogenic cells with 0.0039 ± 0.0005 mGy/MBq, the kidneys with 0.0034 ± 0.0003 mGy/MBq, and the liver with 0.0019 ± 0.0004 mGy/MBq, respectively. No focal tracer uptake suggestive of PCa recurrence could be revealed for any of the patients.

Conclusion

[99mTc]Tc-N4-BTG appears to be a safe diagnostic agent. Compared to GRPR-targeted PET tracers, this 99mTc-labelled SPECT agent could contribute to a broader application and better availability of this novel approach. Further research to assess its clinical value is warranted.