bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating cancer incidence in Uganda: a feasibility study for periodic cancer surveillance research in resource limited settings
Authors: Nakaganda Annet , Spencer Angela , Orem Jackson , Mpamani Collins , Wabinga Henry , Nambooze Sarah , Kiwanuka Gertrude N. , Atwine Raymond , Gemmell Isla , Jones Andrew , Verma Arpana
Published: August 2023

Background

Population based cancer registries (PBCRs) are accepted as the gold standard for estimating cancer incidence in any population. However, only 15% of the world’s population is covered by high quality cancer registries with coverage as low as 1.9% in settings such as Africa. This study was conducted to assess the operational feasibility of estimating cancer incidence using a retrospective “catchment population” approach in Uganda.

Methods

A retrospective population study was conducted in 2018 to identify all newly diagnosed cancer cases between 2013 and 2017 in Mbarara district. Data were extracted from the medical records of health facilities within Mbarara and from national and regional centres that provide cancer care services. Cases were coded according to the International Classification of Diseases for Oncology (ICD-0-03). Data was analysed using CanReg5 and Excel.

Results

We sought to collect data from 30 health facilities serving Mbarara district, southwestern Uganda. Twenty-eight sources (93%) provided approval within the set period of two months. Among the twenty-eight sources, two were excluded, as they did not record addresses for cancer cases, leaving 26 sources (87%) valid for data collection. While 13% of the sources charged a fee, ranging from $30 to $100, administrative clearance and approval was at no cost in most (87%) data sources. This study registered 1,258 new cancer cases in Mbarara district. Of the registered cases, 65.4% had a morphologically verified diagnosis indicating relatively good quality of data. The Age-Standardised Incidence Rates for all cancers combined were 109.9 and 91.9 per 100,000 in males and females, respectively. In males, the most commonly diagnosed cancers were prostate, oesophagus, stomach, Kaposi’s sarcoma and liver. In females, the most common malignancies were cervix uteri, breast, stomach, liver and ovary. Approximately, 1 in 8 males and 1 in 10 females would develop cancer in Mbarara before the age of 75 years.

Conclusion

Estimating cancer incidence using a retrospective cohort design and a “catchment population approach” is feasible in Uganda. Periodic studies using this approach are potentially a precious resource for producing quality cancer data in settings where PBCRs are scarce. This could supplement PBCR data to provide a detailed and comprehensive picture of the cancer burden over time, facilitating the direction of cancer control efforts in resource-limited countries.
Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report
Authors: Xie Hai-Nan , Chen Lan-Lan , Wang Rui , Zhu Zhi-Hong , Huang Hou-Bin
Published: August 2023

Background

Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported.

Case presentation

A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris.

Conclusions

The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.
Harsh parenting and suicide ideation among Chinese adolescents: the roles of self-esteem and school social support
Authors: Zhao Jingfei , Wang Yulong
Published: August 2023

Background

While negative parenting style has considered as a risk factor for suicide ideation, little attention has been given to the mechanisms between harsh parenting and suicide ideation in the context of Chinese culture. This study explored the the potential mediating roles of self-esteem and the potential moderating roles of school social support in the relationship between harsh parenting and suicide ideation among Chinese adolescents.

Methods

We conducted a cross-sectional study among 4189 Chinese adolescents who completed measures of harsh parenting, school social support, self-esteem, and suicide ideation. The moderated mediation model was used to test the roles of self-esteem and school social support on the association between harsh parenting and adolescent suicide ideation.

Results

(1) There were significant positive correlations between harsh parenting and adolescents suicide ideation. (2) Self-esteem mediates the relationship between harsh parenting and suicide ideation in adolescents. (3) School social support moderates the indirect effect of harsh parenting on suicidal ideation.

Conclusions

Beyond the direct impact of harsh parenting, harsh parenting also indirectly contributes to adolescent suicide ideation via the mediator of adolescents’ self-esteem. School social support moderates the relationship between harsh parenting and self-esteem as well as the relationship between self-esteem and suicide ideation. The findings suggest potential pathways for suicide prevention and intervention strategies and highlighted that buffering effect of school social support is limited as risk increasing.
The impact of spectacle correction on the well-being of children with vision impairment due to uncorrected refractive error: a systematic review
Authors: Pirindhavellie Govender-Poonsamy , Yong Ai Chee , Mashige Khathutshelo Percy , Naidoo Kovin S. , Chan Ving Fai
Published: August 2023

Background

Despite being easily corrected with eyeglasses, over two-thirds of the world’s child population presents with vision impairment (VI) due to uncorrected refractive errors. While systematic reviews have shown that VI can significantly impact children’s depression and anxiety, none have reviewed the existing literature on the association between spectacle correction and well-being. This review aims to address this knowledge gap.

Main outcome measures

The main outcome measures were i) cognitive and education well-being which included mathematics and english literacy, reading fluency, school function, academic performance and grades; ii) psychological and mental health well-being which included physical anxiety, learning anxiety and mental health test scores and iii) quality of life.

Methods

We searched eight databases for articles published between 1999 to 2021 that assessed the associations between spectacle correction and children’s (0 to 18 years) well-being. There were no restrictions on language or geographic location. Two reviewers independently screened all publications using validated quality checklists. The findings of the review were analysed using narrative synthesis. [PROSPERO CRD42020196847].

Results

Of 692 records found in the databases, six randomised control trials, one cohort, one cross-sectional and one qualitative study (N = 9, 1.3%) were eligible for analysis. Data were collected from 25 522 children, 20 parents and 25 teachers across the nine studies. Seven were rated as good quality (67 to 100% of quality criteria fulfilled), and two were satisfactory (33 to 66% of quality criteria fulfilled). Spectacle correction was found to improve children’s educational well-being (n = 4 very strong evidence; n = 2 strong evidence), quality of life (n = 1, very strong evidence) and decrease anxiety and increase mental health scores (n = 1, strong evidence).

Conclusion

Evidence suggests that spectacle correction improves children’s cognitive and educational well-being, psychological well-being, mental health, and quality of life. More research is needed, given the paucity of published literature and the focus on only three aspects of well-being.
Association of dietary patterns with general and central obesity among Chinese adults: a longitudinal population-based study
Authors: Zhao Zhongyi , Zhen Shihan , Yan Yumeng , Liu Ning , Ding Ding , Kong Juan
Published: August 2023

Background

Limited evidence exists for the association between dietary patterns and later obesity phenotypes among Chinese adults. This longitudinal study aimed to evaluate associations of dietary patterns with general and central obesity in Chinese adults.

Methods

Based on the China Health and Nutrition Survey (CHNS) waves 2004 and 2015, the study was conducted on 4207 adult men and women (age range: 18–65 years). Dietary intakes were assessed by three consecutive 24-h dietary recalls, and dietary patterns were identified using exploratory factor analysis. Longitudinal associations of dietary patterns with general and central obesity were evaluated using logistic regression analyses.

Results

The prevalence rates of general and central obesity were 14.2% and 42.1%, respectively. Factor analysis extracted three major dietary patterns: “traditional southern,“ “modern,“ and “traditional northern.“ After adjustment for potential confounders, adults in the highest quartile of the traditional southern dietary group were less likely to develop over 10 years general (odds ratio [OR] = 0.50, 95% confidence interval [95%CI]: 0.39, 0.65) and central (OR = 0.52, 95%CI: 0.43, 0.63) obesity compared to those in the lowest quartile group. The modern dietary pattern was not significantly associated with general and central obesity. Adherence to the traditional northern dietary pattern increased the chance of both general and central obesity (OR = 1.61, 95%CI: 1.23, 2.10; OR = 1.64, 95%CI: 1.36, 1.98) after 10 years.

Conclusions

Our study provides longitudinal evidence for associations between dietary patterns and later obesity phenotypes among Chinese adults. Our findings may guide the development of evidence-based preventive nutrition interventions to control the obesity epidemic.
A comparative study of CAD/CAM fabricated polyether ether ketone and fiber-glass reinforcement composites versus metal lingual retainers under vertical load (an in vitro study)
Authors: Alabbadi Abdullah A. , Abdalla Essam M. , Hanafy Seham A. , Yousry Tarek N.
Published: August 2023

Background

Retainer is a necessary procedure when orthodontic treatment complete to avoid relapse due to periodontal fiber elasticity and to allow for alveolar bone regeneration. Compare the influence of vertical force on the failure of three fixed retainers: CAD/CAM polyether ether ketone (PEEK), CAD/CAM fiber glass reinforced composites (FRCs), and lingual retainer wire “Bond-A-Braid™”.

Materials and methods

One hundred and eight maxillary first premolars teeth were randomly allocated to three groups: Group A (CAD/CAM PEEK), Group B (CAD/CAM FRC), and Group C (lingual retainer wire " Bond-A-Braid™”). These retainers were bonded using Assure Plus Bonding Resin and GO TO Paste. For each specimen, a loading cycling and thermocycling machine was used. The failure debonding forces were measured on the interproximal segments using a universal testing machine with a cross-head speed of 1 mm/min. The adhesive remnant index (ARI) was calculated after identifying types of failure with a stereomicroscope at (X 20) magnification.

Results

Group B and group C showed the highest failure bonding forces, with a mean of 209.67 ± 16.15 and 86.81 ± 4.59 N, respectively. However, Group A had a statistically significant lower bond failure force, with a mean value of 45.73 ± 4.48 N. At baseline, there was a statistically significant difference in connector retainer displacement between the three studied groups (p < .001). The ARI score was not statistically significant (p < .001) between the three study groups; for groups A and B, the ARI was predominantly score 3, and group C showed a mixed score of 2 and 3. The failure mode of retainers was investigated using an optical stereomicroscope. In group B, there was a cohesive breakdown in the retainer, and groups A and C exhibited failures primarily in the adhesive at the retainer interface.

Conclusion

All groups differed significantly, with group A having the lowest debonding force and group B having the highest. Furthermore, there was not a substantial variation in ARI, but there was a significant difference in connector retainer displacement and the types of failure amongst the three groups.
A pilot study evaluating the feasibility of assessing undergraduate pharmacy and medical students interprofessional collaboration during an online interprofessional education intervention about hospital discharge
Authors: Almoghirah Hailah , Illing Jan , Nazar Mahdi , Nazar Hamde
Published: August 2023

Background

Interprofessional education (IPE) has been identified as a strategy towards improving competence at interprofessional working and collaboration within teams. Entrustable professional activities (EPAs) provide a framework for translating competencies into elements of clinical practice, some of which in healthcare are inherently interprofessional. However, it is challenging to reconcile that entrustment decisions about student competence in an interprofessional activity are made about an individual without considering the dynamics and tensions between interprofessional team members and the task itself. This can influence students’ development and demonstration of competence at interprofessional collaboration.

Methods

In this study, undergraduate medical and pharmacy students worked in pairs online (Zoom) to undertake the hospital discharge process (a professional activity reliant on interprofessional collaboration) for a simulated patient, producing a hospital discharge letter and completing a consultation with the simulated patient. The online sessions were recorded and interprofessional behaviours were assessed using a validated scale completed by an interprofessional assessment team. Students undertook this IPE intervention three times after receiving feedback and a period of reflection each time.

Results

Eighteen students participated across the entire intervention and 27 one-hour online IPE sessions were completed and recorded. Students demonstrated statistically significant improvements in interprofessional behaviours across the three iterations (p < 0.05 for all the sessions). The discharge letter students produced also improved over the three sessions (p = 0.01). Students found the educational sessions useful and relevant.

Conclusion

This online IPE intervention provided the students with an authentic opportunity to work collaboratively. At the end of each iteration, students received feedback about their work as a team and about the discharge letter, helping students to reflect and purposefully develop their performance. The IPE intervention with this assessment strategy is feasible and allows student development to be captured but has proved to be time and resource intensive.
Person-centred care in nursing homes during the COVID-19 pandemic: a cross sectional study based on nursing staff and first-line managers’ self-reported outcomes
Authors: Lindner Helen , Kihlgren Annica , Pejner Margaretha Norell
Published: August 2023

Background

COVID-19 has presented many difficulties in providing person-centred care (PCC) in nursing homes (NH). Factors such as organisational support, work condition and leadership may play a crucial role in supporting the performance of PCC during COVID restrictions. The study aim was to evaluate nursing staff and manager perceptions of the opportunities to perform person-centred care during the COVID-19 pandemic.

Methods

Nursing staff (NS) (n = 463) and First Line Managers (FLM) (n = 8) within all NHs in one community filled in the SVENIS questionnaire which consists of five areas: perceived organizational support, work climate, person-centred care, work conditions and leadership. A Kruskal-Wallis test was used to perform inter-group comparisons and standard multiple regression was used to investigate which factor contributed most to perform PCC.

Results

The comparison analyses indicate that staff from nursing homes for persons with dementia had the highest opportunities to perform PCC during the pandemic. The day shift staff had more opportunities to perform PCC than night shift staff. The results from the standard multiple regression show that a NA’s current nursing home was the most significant variable affecting the opportunities to perform PCC. The analyses of both the comparison analyses and the regression suggest that day shift staff from nursing homes for persons with dementia had the highest opportunities to perform PCC during the pandemic. The same group also rated the importance of leadership as high for performing PCC.

Conclusion

Despite the COVID-19 restrictions and all the criticism directed against the care of older people; the day staff felt that they conducted PCC. Staff in nursing homes for dementia had the highest opportunities for PCC and this may be because they are better prepared to provide care for the individual in NH. The importance of leadership was also evident, which means that investment in FLMs is seen as necessary.
Regulation of mouse exploratory behaviour by irradiance and cone-opponent signals
Authors: Tamayo E. , Mouland J. W. , Lucas R. J. , Brown T. M.
Published: August 2023

Background

Animal survival depends on the ability to adjust behaviour according to environmental conditions. The circadian system plays a key role in this capability, with diel changes in the quantity (irradiance) and spectral content (‘colour’) of ambient illumination providing signals of time-of-day that regulate the timing of rest and activity. Light also exerts much more immediate effects on behaviour, however, that are equally important in shaping daily activity patterns. Hence, nocturnal mammals will actively avoid light and dramatically reduce their activity when light cannot be avoided. The sensory mechanisms underlying these acute effects of light are incompletely understood, particularly the importance of colour.

Results

To define sensory mechanisms controlling mouse behaviour, we used photoreceptor-isolating stimuli and mice with altered cone spectral sensitivity (Opn1mwR), lacking melanopsin (Opn1mwR; Opn4−/−) or cone phototransduction (Cnga3−/−) in assays of light-avoidance and activity suppression. In addition to roles for melanopsin-dependent irradiance signals, we find a major influence of spectral content in both cases. Hence, remarkably, selective increases in S-cone irradiance (producing a blue-shift in spectrum replicating twilight) drive light-seeking behaviour and promote activity. These effects are opposed by signals from longer-wavelength sensitive cones, indicating a true spectrally-opponent mechanism. Using c-Fos-mapping and multielectrode electrophysiology, we further show these effects are associated with a selective cone-opponent modulation of neural activity in the key brain site implicated in acute effects of light on behaviour, the subparaventricular zone.

Conclusions

Collectively, these data reveal a mechanism whereby blue-shifts in the spectrum of environmental illumination, such as during twilight, promote mouse exploratory behaviour.
Clinical and genetic evaluation of children with short stature of unknown origin
Authors: Zhao Qianqian , Li Yanying , Shao Qian , Zhang Chuanpeng , Kou Shuang , Yang Wanling , Zhang Mei , Ban Bo
Published: August 2023

Background

Short stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin.

Methods

A total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology.

Results

We identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1).

Conclusions

The present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment.
Whole-exome sequencing enables rapid and prenatal diagnosis of inherited skin disorders
Authors: Xintong Zhu , Kexin Zhang , Junwen Wang , Ziyi Wang , Na Luo , Hong Guo
Published: August 2023

Background

Genodermatoses are a broad group of disorders with specific or non-specific skin-based phenotypes, most of which are monogenic disorders. However, it’s a great challenge to make a precise molecular diagnosis because of the clinical heterogeneity. The genetic and clinical heterogeneity brings great challenges for diagnosis in dermatology. The whole exome sequencing (WES) not only expedites the discovery of the genetic variations, but also contributes to genetic counselling and prenatal diagnosis.

Materials and methods

Followed by the initial clinical and pathological diagnosis, genetic variations were identified by WES. The pathogenicity of the copy number variations (CNVs) and single-nucleotide variants (SNVs) were evaluated according to ACMG guidelines. Candidate pathogenic SNVs were confirmed by Sanger sequencing in the proband and the family members.

Results

Totally 25 cases were recruited. Nine novel variations, including c.5546G > C and c.1457delC in NF1, c.6110G > T in COL7A1, c.2127delG in TSC1, c.1445 C > A and c.1265G > A in TYR, Xp22.31 deletion in STS, c.908 C > T in ATP2A2, c.1371insC in IKBKG, and nine known ones were identified in 16 cases (64%). Prenatal diagnosis was applied in 6 pregnant women by amniocentesis, two of whom carried positive findings.

Conclusions

Our findings highlighted the value of WES as a first-tier genetic test in determining the molecular diagnosis. We also discovered the distribution of genodermatoses in this district, which provided a novel clinical dataset for dermatologists.
Development of a novel glycoengineering platform for the rapid production of conjugate vaccines
Authors: Abouelhadid Sherif , Atkins Elizabeth R. , Kay Emily J. , Passmore Ian J. , North Simon J. , Lehri Burhan , Hitchen Paul , Bakke Eirik , Rahman Mohammed , Bossé Janine T. , Li Yanwen , Terra Vanessa S. , Langford Paul R. , Dell Anne , Wren Brendan W. , Cuccui Jon
Published: August 2023

Conjugate vaccines produced either by chemical or biologically conjugation have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccine assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel biotechnological platform that overcomes the limitations of the current conjugate vaccine design method(s). As a model, we focused our design on a leading bioconjugation method using N-oligosaccharyltransferase (OTase), PglB. The installation of MAGIC led to at least twofold increase in glycoconjugate yield via MAGIC when compared to conventional N-OTase based bioconjugation method(s). Then, we improved MAGIC to (a) allow rapid installation of glycoengineering component(s), (b) omit the usage of antibiotics, (c) reduce the dependence on protein induction agents. Furthermore, we show the modularity of the MAGIC platform in performing glycoengineering in bacterial species that are less genetically tractable than the commonly used Escherichia coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against serious bacterial pathogens. We anticipate the utility of the MAGIC platform could enhance vaccines production due to its compatibility with virtually any bioconjugation method, thus expanding vaccine biopreparedness toolbox.
The flavohaemoprotein hmp maintains redox homeostasis in response to reactive oxygen and nitrogen species in Corynebacterium glutamicum
Authors: Jiang Ziqin , Guan Jingyi , Liu Tingting , Shangguan Chunyu , Xu Meijuan , Rao Zhiming
Published: August 2023

Background

During the production of L-arginine through high dissolved oxygen and nitrogen supply fermentation, the industrial workhorse Corynebacterium glutamicum is exposed to oxidative stress. This generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are harmful to the bacteria. To address the issue and to maintain redox homeostasis during fermentation, the flavohaemoprotein (Hmp) was employed.

Results

The results showed that the overexpression of Hmp led to a decrease in ROS and RNS content by 9.4% and 22.7%, respectively, and improved the survivability of strains. When the strains were treated with H2O2 and NaNO2, the RT-qPCR analysis indicated an up-regulation of ammonium absorption and transporter genes amtB and glnD. Conversely, the deletion of hmp gives rise to the up-regulation of eight oxidative stress-related genes. These findings suggested that hmp is associated with oxidative stress and intracellular nitrogen metabolism genes. Finally, we released the inhibitory effect of ArnR on hmp. The Cc-ΔarnR-hmp strain produced 48.4 g/L L-arginine during batch-feeding fermentation, 34.3% higher than the original strain.

Conclusions

This report revealed the influence of dissolved oxygen and nitrogen concentration on reactive species of Corynebacterium glutamicum and the role of the Hmp in coping with oxidative stress. The Hmp first demonstrates related to redox homeostasis and nitrite metabolism, providing a feasible strategy for improving the robustness of strains.
Current status of skin cancers with a focus on immunology and immunotherapy
Authors: Khayyati Kohnehshahri Mahsa , Sarkesh Aila , Mohamed Khosroshahi Leila , HajiEsmailPoor Zanyar , Aghebati-Maleki Ali , Yousefi Mehdi , Aghebati-Maleki Leili
Published: August 2023

Skin cancer is one of the most widespread cancers, with a significant global health effect. UV-induced DNA damage in skin cells triggers them to grow and proliferate out of control, resulting in cancer development. Two common types of skin cancer include melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Melanoma is the most lethal form of skin cancer, and NMSC includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and other forms. The incidence of skin cancer is increasing in part owing to a demographic shift toward an aging population, which is more prone to NMSC, imposing a considerable financial strain on public health services. The introduction of immunostimulatory approaches for cancer cell eradication has led to significant improvements in skin cancer treatment. Over the last three decades, monoclonal antibodies have been used as powerful human therapeutics besides scientific tools, and along with the development of monoclonal antibody production and design procedures from chimeric to humanized and then fully human monoclonal antibodies more than 6 monoclonal antibodies have been approved by the food and drug administration (FDA) and have been successful in skin cancer treatment. In this review, we will discuss the epidemiology, immunology, and therapeutic approaches of different types of skin cancer,
Convolutional neural network-based vocal cord tumor classification technique for home-based self-prescreening purpose
Authors: Kim Gun Ho , Hwang Young Jun , Lee Hongje , Sung Eui-Suk , Nam Kyoung Won
Published: August 2023

Background

In this study, we proposed a deep learning technique that can simultaneously detect suspicious positions of benign vocal cord tumors in laparoscopic images and classify the types of tumors into cysts, granulomas, leukoplakia, nodules and polyps. This technique is useful for simplified home-based self-prescreening purposes to detect the generation of tumors around the vocal cord early in the benign stage.

Results

We implemented four convolutional neural network (CNN) models (two Mask R-CNNs, Yolo V4, and a single-shot detector) that were trained, validated and tested using 2183 laryngoscopic images. The experimental results demonstrated that among the four applied models, Yolo V4 showed the highest F1-score for all tumor types (0.7664, cyst; 0.9875, granuloma; 0.8214, leukoplakia; 0.8119, nodule; and 0.8271, polyp). The model with the lowest false-negative rate was different for each tumor type (Yolo V4 for cysts/granulomas and Mask R-CNN for leukoplakia/nodules/polyps). In addition, the embedded-operated Yolo V4 model showed an approximately equivalent F1-score (0.8529) to that of the computer-operated Yolo-4 model (0.8683).

Conclusions

Based on these results, we conclude that the proposed deep-learning-based home screening techniques have the potential to aid in the early detection of tumors around the vocal cord and can improve the long-term survival of patients with vocal cord tumors.
Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy
Authors: Wan Junlai , He Zhiyi , Peng Renpeng , Wu Xiaopei , Zhu Ziqing , Cui Jiarui , Hao Xiaoxia , Chen Anmin , Zhang Jiaming , Cheng Peng
Published: August 2023

Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1β-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.

Clinical trial registration: Not applciable.

Graphical Abstract
Dendrimer-conjugated isotretinoin for controlled transdermal drug delivery
Authors: Zhao Tianqi , Zhou Mingwei , Wu Ronghui , Wang Huaxin , Zouboulis Christos C. , Zhu Mingji , Lee Myongsoo
Published: August 2023

Background

In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy.

Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D).

Results

Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation.

Conclusion

Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders.

Graphical Abstract
Evaluation of Internet-based pharmaceutical care effect on young and middle-aged patients with hypertension by the principal component analysis and the Markov cohort during COVID-19 pandemic
Authors: Li Xinmei , Xu Wenxiu , Mo Xiaofeng , Wu Fan , Qu Minghong , Ye Junxian , Wu Wenxing , Li Haizhi , Li Te
Published: August 2023

Background

Pharmaceutical care has the potential to improve hypertension control rates in young and middle-aged patients. Due the COVID-19 epidemic, standard intervention methods may not be applicable. We propose establishing an internet-based pharmaceutical care (IPC) route to improve blood pressure control in young and middle-aged patients with hypertension. An evaluation method based on Principal Component Analysis (PCA) and Orthogonal Partial Least-Discriminant Analysis (OPLS-DA) was established to evaluate the effect of the IPC method.

Methods

1) Internet-based Pharmaceutical care (IPC) was provided by pharmacists mainly using Wechat software for one year after enrollment; 2) PCA and OPLS-DA were applied to analyze questionnaire reliability and data variability; 3) Markov cohort was used to evaluate the IPC effect.

Results

Ninety-seven young and middle-aged patients were enrolled. 96 patients received the IPC. 1) The blood pressure control rate increased to 71.88% after IPC in 96 patients. 2) After conducting PCA and OPLS-DA analysis, 10 questions in the questionnaire were significantly improved after the IPC. 3) Markov cohort results showed that patient survival after 28 cycles was 18.62 years and the quality-adjusted life year (QALY) was extended by 5.40 years. The cumulative cost-effectiveness ratio was ¥87.10 per QALY.

Conclusions

The IPC method could significantly improve the blood pressure control rate of patients. The questionnaire analysis method based on PCA and OPLS-DA is an effective method to evaluate the effect of the IPC method. The Markov cohort showed that the IPC had an effect on blood pressure control rate changes. Patients had a strong willingness to pay for IPC.
The FreeD module’s lateral translation timing in the gait robot Lokomat: a manual adaptation is necessary
Authors: Aurich Tabea , van Dellen Florian , Labruyère Rob
Published: August 2023

Background

Pelvic and trunk movements are often restricted in stationary robotic gait trainers. The optional FreeD module of the driven gait orthosis Lokomat offers a combined, guided lateral translation and transverse rotation of the pelvis and may therefore support weight shifting during walking. However, from clinical experience, it seems that the default setting of this timing does not correspond well with the timing of the physiological pelvic movement during the gait cycle. In the software, a manual adaptation of the lateral translation’s timing with respect to the gait cycle is possible. The aim of this study was to investigate if such an offset is indeed present and if a manual adaptation by the therapist can improve the timing towards a more physiological pattern comparable to physiological overground walking.

Methods & Results

Children and adolescents with neurologic gait disorders and a Gross Motor Function Classification System level I-IV completed two different walking conditions (FreeD Default and FreeD Time Offset) in the Lokomat. The medio-lateral center of mass positions were calculated from RGB-Depth video recordings with a marker-less motion capture algorithm. Data of 22 patients (mean age: 12 ± 3 years) were analyzed. Kinematic analyses showed that in the FreeD Default condition, the maximum lateral center of mass excursion occurred too early. In the FreeD Time Offset condition, the manual adaptation by the therapists led to a delay of the maximum center of mass displacement by 8.2% in the first phase of the gait cycle and by 4.9% in the second phase of the gait cycle compared to the FreeD Default condition. The maximum lateral center of mass excursion was closer to that during physiological overground walking in the FreeD Time Offset condition than in the FreeD Default condition.

Conclusion

A manual adaptation of the timing of the FreeD module in the Lokomat shifts pelvis kinematics in a direction of physiological overground walking. We recommend therapists to use this FreeD Time Offset function to adjust the phase of weight shifting for each patient individually to optimize the kinematic walking pattern when a restorative therapy approach is adopted.
Constant ratio between the genomic components of bipartite begomoviruses during infection and transmission
Authors: Xiao Yu-Xin , Li Di , Wu Yi-Jie , Liu Shu-Sheng , Pan Li-Long
Published: August 2023

The genomic components of multipartite viruses are encapsidated in separate virus particles, and the frequencies of genomic components represent one of the key genetic features. Many begomoviruses of economic significance are bipartite, and the details of the association between their genomic components remain largely unexplored. We first analyzed the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of the squash leaf curl China virus (SLCCNV) in plants and found that while the quantities of DNA-A and DNA-B varied significantly during infection, the B/A ratio remained constant. We then found that changes in the B/A ratio in agrobacteria inoculum may significantly alter the B/A ratio in plants at 6 days post inoculation, but the differences disappeared shortly thereafter. We next showed that while the quantities of DNA-A and DNA-B among plants infected by agrobacteria, sap transmission and whitefly-mediated transmission differed significantly, the B/A ratios were similar. Further analysis of gene expression revealed that the ratio of the expression of genes encoded by DNA-A and DNA-B varied significantly during infection. Finally, we monitored the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of another bipartite begomovirus, and a constant B/A ratio was similarly observed. Our findings highlight the maintenance of a constant ratio between the two genomic components of bipartite begomoviruses during infection and transmission, and provide new insights into the biology of begomoviruses.
Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review
Authors: Falkenbach Petra , Raudasoja Aleksi J. , Vernooij Robin W. M. , Mustonen Jussi M. J. , Agarwal Arnav , Aoki Yoshitaka , Blanker Marco H. , Cartwright Rufus , Garcia-Perdomo Herney A. , Kilpeläinen Tuomas P. , Lainiala Olli , Lamberg Tiina , Nevalainen Olli P. O. , Raittio Eero , Richard Patrick O. , Violette Philippe D. , Tikkinen Kari A. O. , Sipilä Raija , Turpeinen Miia , Komulainen Jorma
Published: August 2023

Background

De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research.

Methods

We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool.

Results

We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%).

Conclusion

De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers.

Trial registration

OSF (Open Science Framework):
https://osf.io/ueq32.
MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma
Authors: Pitolli Consuelo , Marini Alberto , Guerra Marika , Pieraccioli Marco , Marabitti Veronica , Palluzzi Fernando , Giacò Luciano , Tamburrini Gianpiero , Cecconi Francesco , Nazio Francesca , Sette Claudio , Pagliarini Vittoria
Published: August 2023

Background

Medulloblastoma (MB) is the most common cerebellar malignancy during childhood. Among MB, MYC-amplified Group 3 tumors display the worst prognosis. MYC is an oncogenic transcription factor currently thought to be undruggable. Nevertheless, targeting MYC-dependent processes (i.e. transcription and RNA processing regulation) represents a promising approach.

Methods

We have tested the sensitivity of MYC-driven Group 3 MB cells to a pool of transcription and splicing inhibitors that display a wide spectrum of targets. Among them, we focus on THZ531, an inhibitor of the transcriptional cyclin-dependent kinases (CDK) 12 and 13. High-throughput RNA-sequencing analyses followed by bioinformatics and functional analyses were carried out to elucidate the molecular mechanism(s) underlying the susceptibility of Group 3 MB to CDK12/13 chemical inhibition. Data from International Cancer Genome Consortium (ICGC) and other public databases were mined to evaluate the functional relevance of the cellular pathway/s affected by the treatment with THZ531 in Group 3 MB patients.

Results

We found that pharmacological inhibition of CDK12/13 is highly selective for MYC-high Group 3 MB cells with respect to MYC-low MB cells. We identified a subset of genes enriched in functional terms related to the DNA damage response (DDR) that are up-regulated in Group 3 MB and repressed by CDK12/13 inhibition. Accordingly, MYC- and CDK12/13-dependent higher expression of DDR genes in Group 3 MB cells limits the toxic effects of endogenous DNA lesions in these cells. More importantly, chemical inhibition of CDK12/13 impaired the DDR and induced irreparable DNA damage exclusively in MYC-high Group 3 MB cells. The augmented sensitivity of MYC-high MB cells to CDK12/13 inhibition relies on the higher elongation rate of the RNA polymerase II in DDR genes. Lastly, combined treatments with THZ531 and DNA damage-inducing agents synergically suppressed viability of MYC-high Group 3 MB cells.

Conclusions

Our study demonstrates that CDK12/13 activity represents an exploitable vulnerability in MYC-high Group 3 MB and may pave the ground for new therapeutic approaches for this high-risk brain tumor.
Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty
Authors: Brambilla Ilaria , Guarracino Carmen , Pistone Carmelo , Klersy Catherine , Licari Amelia , Marseglia Gian Luigi , Tondina Enrico
Published: August 2023

Background

Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation.

Methods

The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up).

Results

Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23–0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 − 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control.

Conclusions

uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.