bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a neuromuscular joint-protective exercise therapy program for treatment of wrist osteoarthritis: a randomized controlled trial
Authors: Larsson Sara L. , Ekstrand Elisabeth , Dahlin Lars B. , Björkman Anders , Brogren Elisabeth
Published: January 2024

Background

Individuals with wrist osteoarthritis (OA) can suffer from pain, muscular weakness, and impaired motion of the wrist, which can reduce the quality of life. While there is strong evidence that all patients with OA should receive first-line treatment with education and exercises, this approach has not yet been proposed for individuals with wrist OA. Therefore, this trial aimed to evaluate the effectiveness of a first line neuromuscular joint-protective exercise therapy program compared to a training program with range of motion (ROM) exercises in patients with wrist OA.

Methods

In this randomized controlled trial (RCT), 48 patients with symptomatic and radiographically confirmed wrist OA were randomly allocated to a 12-week self-management program with either a neuromuscular joint-protective exercise therapy program (intervention group) or a training program with ROM exercises only (control group). Our primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) with secondary outcome measures of grip strength, range of wrist motion, the Numerical Pain Rating, Scale (NPRS), the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Generalized Self-Efficacy Scale (GSES). The outcome measures were evaluated by a blinded assessor at baseline and 12 weeks. Between-groups differences were analyzed using the Mann–Whitney U test and within-group differences were analyzed with the Wilcoxon signed-rank test.

Results

A total of 41 participants were analyzed at 12 weeks. There were no significant differences in PRWE between the groups at 12 weeks (p = 0.27). However, DASH improved significantly in the intervention group compared to the control group (p = 0.02) and NPRS on load within the intervention group (p = 0.006). The difference in DASH should be interpreted with caution since it could be due to a non-significant increase (worsening) from baseline in the control group in combination with a non-significant decrease (improvement) in the intervention group.

Conclusions

This RCT showed that the novel neuromuscular joint-protective exercise therapy program was not superior in reducing pain and improving function compared to a training program with ROM exercises at 12 weeks. Future research is warranted to evaluate the effectiveness of forthcoming exercise therapy treatment programs for patients with wrist OA.

Trial registration

ClinicalTrials.gov, NCT05367817. Retrospectively registered on 10/05/2022. https://clinicaltrials.gov.
Trends and projection of forearm fractures including elbow fractures of the Olecranon in Sweden: an analysis of 363 968 fractures using public aggregated data
Authors: Axenhus Michael , Svedman Simon , Magnéli Martin
Published: January 2024

Background

Forearm and olecranon fractures are a common orthopaedic injury. This study aimed to analyse whether the incidence of forearm injury is changing and identifying trends in the number of forearm and olecranon fractures using public aggregated data in Sweden.

Methods

The number of forearm and olecranon fractures as defined by the number of registered diagnoses with the ICD-10 code of S52 were collected and normalized per 100,000 inhabitants and stratified per sex, age, and month. Age-adjusted incidence for forearm and olecranon fractures were calculated using the direct method. Poisson regression was used to analyse monthly, seasonal and yearly change in forearm and olecranon fracture incidence. Logistical regression was used to predict future trends of forearm and olecranon fractures.

Results

The findings revealed a slight decreasing trend in forearm and olecranon fractures. The average incidence rate during the study period was 333 with women having a higher incidence rate than men. More fractures occurred in the winter months. Fluctuations in the number of forearm and olecranon fractures were observed during 2020 which may be influenced by the COVID-19 pandemic. Based on current data, forearm and olecranon fractures are expected to decrease in Sweden by 2035.

Conclusion

This study describes the trend of forearm and olecranon fractures among individuals according to sex and age in Sweden using easily obtainable data. Trends in forearm and olecranon fractures are dependent on sex and age but generally show a decreasing trend. More precise studies are needed in order to properly quantify the specific incidence of various subtypes of forearm and olecranon fractures and associated risk factors.
Impact of orthodontic-induced facial morphology changes on aesthetic evaluation: a retrospective study
Authors: Liu Chao , Du Siyuan , Wang Zhengliang , Guo Shikai , Cui Mengjuan , Zhai Qianglan , Zhang Manfei , Fang Bing
Published: January 2024

Background

The profound influence of orthodontic treatments on facial aesthetics has been a topic of increasing interest. This study delves into the intricate interplay between orthodontic treatments, facial feature alterations, and aesthetic perceptions.

Methods

A total of 73 patients who had undergone orthodontic treatment were included in this study. Facial photographs were taken before and after treatment. Ten orthodontists provided facial aesthetic ratings (FAR) for each patient's frontal, profile, and overall views. 48 facial landmarks were manually placed by the orthodontists and normalized using Generalized Procrustes analysis (GPA). Two types of phenotypes were derived from facial landmarks. Global facial phenotypes were then extracted using principal component analysis (PCA). Additionally, 37 clinical features related to aesthetics and orthodontics were extracted. The association between facial features and changes in FAR after orthodontic treatment was determined using these two types of phenotypes.

Results

The FAR exhibited a high correlation among orthodontic experts, particularly in the profile view. The FAR increased after orthodontic treatment, especially in profile views. Extraction of premolars and orthognathic surgery were found to result in higher FAR change. For global facial phenotypes, the most noticeable changes in the frontal and profile views associated with FAR occurred in the lip area, characterized by inward retraction of the lips and slight chin protrusion in the profile view, as well as a decrease in lip height in the frontal view. The changes observed in the profile view were statistically more significant than those in the frontal view. These facial changes were consistent with the changes from orthodontic treatment. For clinical features, two profile features, namely pg.sm.hori and pg.n.ls, were found to be associated with FAR following orthodontic treatment. The highest FAR scores were achieved when pg.sm.hori was at 80° and pg.n.ls was at 8°. On the other hand, frontal clinical features had a subtle effect on FAR during orthodontic treatment.

Conclusions

This study demonstrated that orthodontic treatment improves facial aesthetics, particularly at lip aera in the profile view. Profile clinical features, such as pg.sm.hori and pg.n.ls, are essential in orthodontic treatment which could increase facial aesthetics.
Board game on sexually transmitted infections for imprisoned women
Authors: da Silva Carvalho Isaiane , Mendes Ryanne Carolynne Marques Gomes , de Souza Soares Lima Laís Helena , da Silva Gabrielle Pessôa , de Freitas Gonçalves Lima Monique , Guedes Tatiane Gomes , Linhares Francisca Márcia Pereira
Published: January 2024

Introduction

The board games is an educational technology that represents an appealing, active and playful pedagogical strategy and may be capable of motivating imprisoned women to learn about Sexually Transmitted Infections.

Methods

A methodological study to develop and evaluate a board game, following these stages: 1. Integrative literature review to identify educational technologies on Sexually Transmitted Infections used by imprisoned women; 2. Development of the board game; and 3. Content validation performed by 23 evaluators and semantic evaluation carried out with 10 imprisoned women who were enrolled in a school located within a female prison unit in the city of Recife, state of Pernambuco, Brazil.

Results

The board game consisted of the following: 01 board; 01 instructions manual; 05 pawns; 52 cards; and 01 dice. A global Content Validity Index of 0.966 was reached in the content validation process performed by health and education professionals. In the validation of the board game content regarding appearance, performed by designers/developers, most of the items obtained a Content Validity Coefficient below 0.85, which resulted in the need for adjustments and a new validation round with these professionals, in which Content Validity Coefficient = 0.917 was obtained. In the semantic evaluation, all the women stated that they improved their knowledge, increased their motivation to attend the class and would like to play the board game again.

Conclusions

The “Previna” board game has been validated and can be considered an important pedagogical tool in the construction of knowledge in relation to the prevention, treatment and control of Sexually Transmitted Infections in the female prison context. The quality of this educational technology is directly related to its development based on an appropriate theoretical and methodological framework, in addition to satisfactory feedback from the target audience.

Trial registration

Not applicable.
Integrated virtual simulation and face-to-face simulation for clinical judgment training among undergraduate nursing students: a mixed-methods study
Authors: Yang Jian , Zhou Wen Jie , Zhou Si Chen , Luo Dan , Liu Qian , Wang Ai-Ling , Yu Si-Hong , Zhu Xiao-Ping , He Xue Yu , Hu Fen , Yang Bing Xiang , Chen Jie
Published: January 2024

Background

Virtual simulation and face-to-face simulation are effective for clinical judgment training. Rare studies have tried to improve clinical judgment ability by applying virtual simulation and face-to-face simulation together. This study aimed to evaluate the effect of an integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program on enhancing nursing students’ clinical judgment ability and understanding of nursing students’ experiences of the combined simulation.

Methods

A sequential exploratory mixed-methods study was conducted in a nursing simulation center of a university in Central China. Third-year nursing students (n = 122) taking clinical training in ICUs were subsequentially assigned to the integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program arm (n = 61) or the face-to-face simulation-only arm (n = 61) according to the order in which they entered in ICU training. Clinical judgment ability was measured by the Lasater Clinical Judgment Rubric (LCJR). Focus group interviews were conducted to gather qualitative data.

Results

Students in both arms demonstrated significant improvement in clinical judgment ability scores after simulation, and students in the integrated arm reported more improvement than students in the face-to-face simulation-only arm. The qualitative quotes provided a context for the quantitative improvement measured by the LJCR in the integrated arm. Most of the quantitative findings were confirmed by qualitative findings, including the domains and items in the LJCR. The findings verified and favored the effect of the combination of non-immersive virtual simulation and high-fidelity face-to-face simulation integrated program on enhancing nursing students’ clinical judgment ability.

Conclusions

The integrated virtual simulation and face-to-face simulation program was feasible and enhanced nursing students’ self-reported clinical judgment ability. This integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program may benefit nursing students and newly graduated nurses in the ICU more than face-to-face simulation only.
Spirulina platensis as a growth booster for broiler; Insights into their nutritional, molecular, immunohistopathological, and microbiota modulating effects
Authors: Abdelfatah Samar H. , Yassin Aya M. , Khattab Marwa S. , Abdel-Razek Ahmed S. , Saad Adel H.
Published: January 2024

Background

The present study is designed to assess the effect of adding various doses of Spirulina platensis (SP) on broiler chicken growth performance, gut health, antioxidant biomarkers, cecal microbiota, histopathology, and immunohistochemistry of inducible nitric oxide synthase (iNOS). 240 male Cobb 500 broiler chicks (1 day old) were placed into four groups (sixty birds/group), then each group was further divided into three replicates of 20 chickens each for 35 days. Birds were allocated as follows; the 1st group (G1), the control group, fed on basal diet, the 2nd group (G2): basal diet plus SP (0.1%), the 3rd group (G3): basal diet plus SP (0.3%), and the 4th group (G4): basal diet plus SP (0.5%).

Results

Throughout the trial (d 1 to 35), SP fortification significantly increased body weight growth (BWG) and feed conversion rate (FCR) (P < 0.05). Bursa considerably increased among the immunological organs in the Spirulina-supplemented groups. Within SP-supplemented groups, there was a substantial increase in catalase activity, blood total antioxidant capacity, jejunal superoxide dismutase (SOD), and glutathione peroxidase (GPX) activity (P < 0.05). Fatty acid binding protein 2 (FABP2), one of the gut barrier health biomarkers, significantly increased in the SP-supplemented groups but the IL-1β gene did not significantly differ across the groups (P < 0.05). Different organs in the control group showed histopathological changes, while the SP-supplemented chicken showed fewer or no signs of these lesions. The control group had higher levels of iNOS expression in the gut than the SP-supplemented groups (p < 0.05). Cecal Lactobacillus count significantly elevated with increasing the rate of SP inclusion rate (p < 0.05).

Conclusion

Supplementing broiler diets with SP, particularly at 0.5%, can improve productivity and profitability by promoting weight increase, feed utilization, antioxidant status, immunity, and gastrointestinal health.
Enhanced protein secretion in reduced genome strains of Streptomyces lividans
Authors: Hamed Mohamed Belal , Busche Tobias , Simoens Kenneth , Carpentier Sebastien , Kormanec Jan , Van Mellaert Lieve , Anné Jozef , Kalinowski Joern , Bernaerts Kristel , Karamanou Spyridoula , Economou Anastassios
Published: January 2024

Background

S. lividansTK24 is a popular host for the production of small molecules and the secretion of heterologous protein. Within its large genome, twenty-nine non-essential clusters direct the biosynthesis of secondary metabolites. We had previously constructed ten chassis strains, carrying deletions in various combinations of specialized metabolites biosynthetic clusters, such as those of the blue actinorhodin (act), the calcium-dependent antibiotic (cda), the undecylprodigiosin (red), the coelimycin A (cpk) and the melanin (mel)clusters, as well as the geneshrdD, encoding a non-essential sigma factor, andmatAB, a locus affecting mycelial aggregation. Genome reduction was aimed at reducing carbon flow toward specialized metabolite biosynthesis to optimize the production of secreted heterologous protein.

Results

Two of theseS. lividansTK24 derived chassis strains showed ~ 15% reduction in biomass yield, 2-fold increase of their total native secretome mass yield and enhanced abundance of several secreted proteins compared to the parental strain. RNAseq and proteomic analysis of the secretome suggested that genome reduction led to cell wall and oxidative stresses and was accompanied by the up-regulation of secretory chaperones and ofsecDF, a Sec-pathway component. Interestingly, the amount of the secreted heterologous proteins mRFP and mTNFα, by one of these strains, was 12 and 70% higher, respectively, than that secreted by the parental strain.

Conclusion

The current study described a strategy to construct chassis strains with enhanced secretory abilities and proposed a model linking the deletion of specialized metabolite biosynthetic clusters to improved production of secreted heterologous proteins.
Diagnosis and management of infertility: NICE-adapted guidelines from the Italian Society of Human Reproduction
Authors: Palomba Stefano , Viganò Paola , Chamayou Sandrine , Donarelli Zaira , Costantini Maria Paola , Marci Roberto , Piomboni Paola , Fino Egidio , Montano Luigi , Guglielmino Antonino , Somigliana Edgardo ,   and the SIRU Working Group on Italian Guideline for Infertility, Arrighi Nicola , Biallo Anna , Boeri Luca , Cinotti Antonella , Coccia Elisabetta , D’Amico Giacomo , Di Matteo Cinzia , Favilla Vincenzo , Antonino Guglielmino , Minasi Maria Giulia , Ricciuto Veronica , Sbracia Marco , Spinella Francesca , Vitale Maria , Zinno Giulia Eleonora Carmela
Published: January 2024

In Italy the fertility rate is very low, and an increasing number of patients are infertile and require treatments. The Italian Law concerning the safety of patient care, and the professional liability of health professionals, indicates that health professionals must comply with the recommendations set out in the guidelines developed by public and private bodies and institutions, as well as scientific societies and technical-scientific associations of the health professions, except for specific cases. Unfortunately, no guideline for the diagnosis and the management of infertility is currently available in Italy. In 2019, the Italian Society of Human Reproduction pointed out the need to produce Italian guidelines and subsequently approved the establishment of a multidisciplinary and multiprofessional working group (MMWG) to develop such a guideline. The MMWG was representative of 5 scientific societies, one national federation of professional orders, 3 citizens' and patients' associations, 5 professions (including lawyer, biologist, doctor, midwife, and psychologist), and 3 medical specialties (including medical genetics, obstetrics and gynecology, and urology). The MMWG chose to adapt a high-quality guideline to the Italian context instead of developing one from scratch. Using the Italian version of the Appraisal of Guidelines for Research and Evaluation II scoring system, the National Institute of Clinical Excellence guidelines were selected and adapted to the Italian context. The document was improved upon by incorporating comments and suggestions where needed. This study presents the process of adaptation and discusses the pros and cons of the often-neglected choice of adapting rather than developing new guidelines.
R-spondin-1 induces Axin degradation via the LRP6-CK1ε axis
Authors: Tan Lifeng , Yan Mengfang , Su Zijie , Wang Hanbin , Li Huan , Zhao Xibao , Liu Shanshan , Zhang Long , Sun Qi , Lu Desheng
Published: January 2024

R-spondins (RSPOs) are secreted signaling molecules that potentiate the Wnt/β-catenin pathway by cooperating with Wnt ligands. RSPO1 is crucial in tissue development and tissue homeostasis. However, the molecular mechanism by which RSPOs activate Wnt/β-catenin signaling remains elusive. In this study, we found that RSPOs could mediate the degradation of Axin through the ubiquitin–proteasome pathway. The results of Co-IP showed that the recombinant RSPO1 protein promoted the interaction between Axin1 and CK1ε. Either knockout of the CK1ε gene or treatment with the CK1δ/CK1ε inhibitor SR3029 caused an increase in Axin1 protein levels and attenuated RSPO1-induced degradation of the Axin1 protein. Moreover, we observed an increase in the number of associations of LRP6 with CK1ε and Axin1 following RSPO1 stimulation. Overexpression of LRP6 further potentiated Axin1 degradation mediated by RSPO1 or CK1ε. In addition, recombinant RSPO1 and Wnt3A proteins synergistically downregulated the protein expression of Axin1 and enhanced the transcriptional activity of the SuperTOPFlash reporter. Taken together, these results uncover the novel mechanism by which RSPOs activate Wnt/β-catenin signaling through LRP6/CK1ε-mediated degradation of Axin.

Graphical Abstract
A20 haploinsufficiency in a neonate caused by a large deletion on chromosome 6q
Authors: Zhang Fan , Zhang Liang
Published: January 2024

Haploinsufficiency of A20 (HA20) is a rare monogenic disease caused by heterozygous loss-of-function mutations in the tumor necrosis factor alpha-induced protein 3 (TNFAIP3) gene located on chromosome 6q23.3. The majority of disease-causing mutations in most cases of HA20 comprise single nucleotide variations, small insertions, or deletions in TNFAIP3, which result in a premature termination codon and subsequent disruption of its anti-inflammatory role. Large deletions have been reported sporadically. HA20 patients may present with a variety of autoinflammatory and autoimmune features during early childhood; however, cases with neonatal onset are rare. Here, we describe a Chinese neonate presenting with concomitant inflammatory and other syndromic manifestations caused by a 5.15 Mb interstitial deletion in chromosome 6; these deletions affect TNFAIP3. Taken together, the data extend the clinical and genetic spectra of HA20.
Tocilizumab for treating mevalonate kinase deficiency and TNF receptor-associated periodic syndrome: a case series and literature review
Authors: Li Yandie , Lu Meiping
Published: January 2024

Background

Mevalonate kinase deficiency (MKD) and TNF receptor-associated periodic syndrome (TRAPS) are categorized as systemic autoinflammatory diseases (SAIDs), which are rare diseases characterized by early onset, severe conditions, and challenging diagnosis and treatment. Although different SAIDs have varying standard treatments, some SAIDs are poorly controlled after routine treatment, seriously affecting the growth and development of children and their quality of life. This study aims to provide more treatment strategies for SAIDs.

Case presentation

We present two Chinese patients with MKD and TRAPS who were resistant to TNF- (tumor necrosis factor-) α blockade. After using etanercept, baricitinib, and glucocorticoid, patients with MKD and TRAPS still had periodic fever and rash. Due to the unavailability of IL-1 antagonists in the Chinese Mainland, we started administering intravenous tocilizumab (TCZ) at a dosage of 240 mg every three weeks. They had not experienced fever or rash after receiving one or two doses of TCZ. Before treatment with TCZ in the MKD patient, white blood cell (WBC) count, and TNF-α level were normal, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) increased significantly, and IL-6 increased slightly. After treatment with TCZ, ESR and CRP levels returned to normal; however, IL-6 increased occasionally. In the TRAPS patient, ESR, CRP, WBC, IL-6, and TNF-α levels were increased significantly. After TCZ treatment, ESR, CRP, WBC, IL-6, and TNF-α levels returned to normal. The two patients were treated with TCZ for more than six months and achieved clinical and serological remission. Furthermore, they had no adverse reactions after injection of TCZ.

Conclusion

In the absence of IL-1 antagonists in mainland China, tocilizumab emerges as an alternative drug in SAIDs that are resistant to TNF-α blockade.
Comparison of efficacy between endoscope-assisted anterior cervical discectomy and fusion (ACDF) and open ACDF in the treatment of single-segment cervical spondylotic myelopathy
Authors: Wu Zhi-Peng , Wei Zhao-yong , Song Xiao-Lei
Published: January 2024

Background

In this study, we compared the clinical efficacy of endoscope-assisted anterior cervical discectomy and fusion (ACDF) with open ACDF in the treatment of single-segment cervical spondylotic myelopathy.

Methods

A retrospective analysis was performed on 52 patients with single-segment cervical spondylotic myelopathy between June 2021 and February 2022, including 33 males and 19 females, with a mean age of 58.42 ± 9.26) years. Among them, 28 patients were treated with endoscope-assisted ACDF (Group A), including 2 cases of C4/5 segment, 16 cases of C5/6 segment, and 10 cases of C6/7 segment; 24 patients were treated with open ACDF (Group B), including 4 cases of C4/5 segment, 11 cases of C5/6 segment, and 9 cases of C6/7 segment. The operation time, intraoperative blood loss, hospital stay, and complications were recorded and compared between the two groups. The Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association (JOA) score were used for clinical evaluation during the follow-up in the 1st month and 3rd month after surgery, and at the final follow-up.

Results

The 52 patients were followed up on average for 13.04 months (12–17 months). The operation time in Group A and Group B was (105.18 + 8.66) minutes and (81.88 + 6.05) minutes, the intraoperative blood loss was (84.29 + 13.45) mL and (112.92 + 17.81) mL, and the hospital stay was (6.75 + 1.29) days and (7.63 + 1.41) days, respectively. The difference between the two groups was statistically significant (P < 0.05). The VAS and JOA scores in the 1st month and the 3rd month after surgery and the last follow-up significantly improved in both groups compared with those before surgery (P < 0.05). The VAS and JOA scores of Group A in the 1st month, 3rd month after surgery, and the last follow-up were better than those in Group B (P < 0.05). The complication rate in Group A was 7% (2/28), which was not significantly different from the 17% (4/24) in Group B (P > 0.05).

Conclusion

Both endoscope-assisted ACDF and open ACDF can achieve satisfactory clinical efficacy in the treatment of single-segment cervical spondylotic myelopathy. Although the operation time of endoscope-assisted ACDF is prolonged, it has the advantages of clear vision, thorough decompression, less blood loss, and reduced risk of nerve damage, and is worthy of clinical promotion and application.
Comparison of clinical outcomes between sequestered cervical disk herniation and non-sequestered cervical disk herniation after anterior cervical decompression and fusion: a cohort study
Authors: Jin Lanbo , Sun Ke , Liu Gang , Yuan Wen , Chen Huajiang , Tian Ye
Published: January 2024

Background

The advantages of anterior cervical decompression and fusion (ACDF) were well published, while research on postoperative results in different subtypes of cervical disk herniation (CDH) still remains blank. This study aimed to explore the surgical outcome between sequestration and other types in CDH.

Methods

This retrospective cohort study enrolled 108 patients treated with ACDF in our hospital. The participants were divided into two groups according to the existence of a sequestered disk. The Visual analog scale score, the Japanese Orthopedics Association (JOA) score and the Neck disability index score were used to evaluate postoperative outcome.

Results

Significant improvements were observed in both groups at every viewpoint (P < 0.001). The mean JOA was 15.04 ± 1.26 in the sequestered disk group and 14.45 ± 1.43 in the non-sequestered disk group two months after the operation (P = 0.026 < 0.05). The improvement in JOA at two months after ACDF showed a significant difference: 46.58% ± 39.17% in the sequestered disk group and 33.39% ± 28.82% in the non-sequestered disk group (P = 0.047 < 0.05). Thirty-two patients in the sequestered disk group (64%) and 19 patients in the non-sequestered disk group (32.76%) presented with high signal intensity of the spinal cord on preoperative cervical T2-weighted MRI (P < 0.001).

Conclusions

Patients with sequestered cervical disks seemed to have a higher degree of symptom improvement two months after ACDF. CDH with a sequestered disk appears to be more likely to cause high signal intensity changes in the compressed cervical spine on T2-weighted MRI. We prefer early positive surgery in patients with sequestered cervical disks from the clinical point of view.
Impact of lipodystrophy on health-related quality of life: the QuaLip study
Authors: Demir Tevfik , Simsir Ilgin Yildirim , Tuncel Ozlem Kuman , Ozbaran Burcu , Yildirim Ilker , Pirildar Sebnem , Ozen Samim , Akinci Baris
Published: January 2024

Background

Lipodystrophy is a rare disease characterized by loss of adipose tissue. Natural history studies have demonstrated significant burden of disease; however, there is limited data on the impact of lipodystrophy on quality of life (QoL) and psychoemotional well-being. The QuaLip study is a prospective observational real-world study that aims to determine the impact of lipodystrophy on QoL and psychoemotional well-being and explore subjective burden of the disease. Sixty-seven adult patients and eight pediatric patients with lipodystrophy were included. Patients were followed up for 24 months and assessments were repeated every three months. Patients were examined by licensed psychiatrists at baseline, and at year 1 and year 2 visits.

Results

Eighteen (27.69%) of 65 adult patients (two subjects refused psychiatric assessment) were diagnosed with a psychiatric disorder (e.g., depressive episodes, mixed anxiety and depressive disorder, anxiety disorder, adjustment disorder, recurrent depression, panic disorder, generalized anxiety disorder, unspecified mood disorder, nonorganic sleep disorder, post-traumatic stress disorder, depressive episode comorbidity, social phobia and obsessive–compulsive disorder comorbidity). Lipodystrophy disease and QoL questionnaires revealed a significant disease burden over the study period. More than one-third of patients reported depression symptoms on the Beck Depression Inventory and more than one-fourth of the patients reported significant hunger throughout the study period. Physical appearance, fatigue, and pain contributed to the disease burden. QoL scores were lower in patients with psychiatric disease and in those with poor metabolic control. Attention deficit hyperactivity disorder, depressive disorder, sub-threshold depressive symptoms, obsessive–compulsive disorder, appetite problems, and issues with physical appearance were identified in selected pediatric subjects.

Conclusions

Lipodystrophy has a significant impact on QoL and psychoemotional well-being. Psychiatric disorders seem to be underdiagnosed among patients with lipodystrophy.
Design of mobile and website health application devices for drug tolerability in hereditary fructose intolerance
Authors: Izquierdo-García Elsa , Lázaro-Cebas Andrea , Montero Pastor Berta , Such Díaz Ana , Álvaro-Alonso Elena Alba , López Guerra Laura , Escobar-Rodríguez Ismael
Published: January 2024

Background

Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance.

Results

A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals.

Conclusions

IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.
Post-quake call for action: developing core competencies matrix for Syrian health workers in emergency time
Authors: Saeed Hani , Hamid Sulaf , Zoukar Imad , Khiami Adel , Al Hawat Lama , Khoja Mohammed , Khawatmy Hossam , Abdalnour Hani , Dashash Mayssoon
Published: January 2024

Background

The recent earthquake in Syria has caused widespread devastation, leading to extensive damage and loss of life. Considering the diverse range of disasters and conflicts that have affected Syrian society, health workers must possess essential competencies to effectively manage various types of disasters, including earthquakes. Therefore, this study was undertaken to identify the specific competencies required by Syrian health workers to respond efficiently and effectively to earthquakes.

Methods

An exploratory qualitative study was conducted at the Medical Education Program MEP of the Syrian Virtual University SVU. Nine members of the research team of the MEP, who represent various health specializations in medicine, dentistry, nursing, and pharmacy, accepted to take part in this study. Among these, three members have been actively involved in providing health care in hospitals and the field during the Syrian earthquake on 6 February 2023. The Delphi process was adopted to identify competencies. Health workers involved in earthquake response were categorized into nine groups including medical doctors, dentists, pharmacists, nurses, psychological support professionals, medical students, allied healthcare professionals, on-site disaster teams, and managers. The final list was accepted if it achieved more than 80% agreement among the participants in the first, second, and final rounds.

Results

The study identified 74 competencies (12 knowledge items, 35 skills, and 27 attitudes) essential for health workers to respond effectively to earthquakes. They are categorized into five domains: "Preparing the team for the rescue process during and, after earthquakes, Implementation of the rescue process, Education and psychological support, Research, and development".

Conclusion

A list of earthquake competencies was identified for health workers. It is hoped that this list will enhance a country’s resilience and will enable decision–makers to support health workers in acquiring these competencies within a very strained health system in Syria and other countries.
Machine learning approaches to identify systemic lupus erythematosus in anti-nuclear antibody-positive patients using genomic data and electronic health records
Authors: Chung Chih-Wei , Chou Seng-Cho , Hsiao Tzu-Hung , Zhang Grace Joyce , Chung Yu-Fang , Chen Yi-Ming
Published: January 2024

Background

Although the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) has required at least a positive anti-nuclear antibody (ANA) titer (≥ 1:80), it remains challenging for clinicians to identify patients with SLE. This study aimed to develop a machine learning (ML) approach to assist in the detection of SLE patients using genomic data and electronic health records.

Methods

Participants with a positive ANA (≥ 1:80) were enrolled from the Taiwan Precision Medicine Initiative cohort. The Taiwan Biobank version 2 array was used to detect single nucleotide polymorphism (SNP) data. Six ML models, Logistic Regression, Random Forest (RF), Support Vector Machine, Light Gradient Boosting Machine, Gradient Tree Boosting, and Extreme Gradient Boosting (XGB), were used to identify SLE patients. The importance of the clinical and genetic features was determined by Shapley Additive Explanation (SHAP) values. A logistic regression model was applied to identify genetic variations associated with SLE in the subset of patients with an ANA equal to or exceeding 1:640.

Results

A total of 946 SLE and 1,892 non-SLE controls were included in this analysis. Among the six ML models, RF and XGB demonstrated superior performance in the differentiation of SLE from non-SLE. The leading features in the SHAP diagram were anti-double strand DNA antibodies, ANA titers, AC4 ANA pattern, polygenic risk scores, complement levels, and SNPs. Additionally, in the subgroup with a high ANA titer (≥ 1:640), six SNPs positively associated with SLE and five SNPs negatively correlated with SLE were discovered.

Conclusions

ML approaches offer the potential to assist in diagnosing SLE and uncovering novel SNPs in a group of patients with autoimmunity.
Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks
Authors: Stitzlein Lea M. , Adams Jack T. , Stitzlein Erin N. , Dudley Richard W. , Chandra Joya
Published: January 2024

Targeted therapies, including small molecule inhibitors directed against aberrant kinase signaling and chromatin regulators, are emerging treatment options for high-grade gliomas (HGG). However, when translating these inhibitors into the clinic, their efficacy is generally limited to partial and transient responses. Recent studies in models of high-grade gliomas reveal a convergence of epigenetic regulators and kinase signaling networks that often cooperate to promote malignant properties and drug resistance. This review examines the interplay between five well-characterized groups of chromatin regulators, including the histone deacetylase (HDAC) family, bromodomain and extraterminal (BET)-containing proteins, protein arginine methyltransferase (PRMT) family, Enhancer of zeste homolog 2 (EZH2), and lysine-specific demethylase 1 (LSD1), and various signaling pathways essential for cancer cell growth and progression. These specific epigenetic regulators were chosen for review due to their targetability via pharmacological intervention and clinical relevance. Several studies have demonstrated improved efficacy from the dual inhibition of the epigenetic regulators and signaling kinases. Overall, the interactions between epigenetic regulators and kinase signaling pathways are likely influenced by several factors, including individual glioma subtypes, preexisting mutations, and overlapping/interdependent functions of the chromatin regulators. The insights gained by understanding how the genome and epigenome cooperate in high-grade gliomas will guide the design of future therapeutic strategies that utilize dual inhibition with improved efficacy and overall survival.
Improving access to family planning for women with disabilities in Kaduna city, Nigeria: study protocol for a pragmatic cluster-randomized controlled trial with integrated process evaluation
Authors: Marks Sarah , Arogundade Ekundayo , Carew Mark T. , Chen Shanquan , Banks Lena Morgon , Kuper Hannah , Adegoke Femi , Davey Calum
Published: January 2024

Background

Globally, women with disabilities are less likely to have access to family planning services compared to their peers without disabilities. However, evidence of effective interventions for promoting their sexual and reproductive health and rights remains limited, particularly in low- and middle-income settings. To help address disparities, an inclusive sexual and reproductive health project was developed to increase access to modern contraceptive methods and reduce unmet need for family planning for women of reproductive age with disabilities in Kaduna city, Nigeria. The project uses demand-side, supply-side and contextual interventions, with an adaptive management approach. This protocol presents a study to evaluate the project’s impact.

Methods

A pragmatic cluster-randomized controlled trial design with surveys at baseline and endline will be used to evaluate interventions delivered for at least 1 year at health facility and community levels in comparison to ‘standard’ state provision of family planning services, in the context of state-wide and national broadcast media and advocacy. Randomization will be conducted based on the health facility catchment area, with 19 clusters in the intervention arm and 18 in the control arm. The primary outcome measure will be access to family planning. It was calculated that at least 950 women aged 18 to 49 years with disabilities (475 in each arm) will be recruited to detect a 50% increase in access compared to the control arm. For each woman with disabilities enrolled, a neighbouring woman without disabilities in the same cluster and age group will be recruited to assess whether the intervention has a specific effect amongst women with disabilities. The trial will be complemented by an integrated process evaluation. Ethical approval for the study has been given by the National Health Research Ethics Committee of Nigeria and London School of Hygiene & Tropical Medicine.

Discussion

Defining access to services is complex, as it is not a single variable that can be measured directly and need for family planning is subjectively defined. Consequently, we have conceptualized ‘access to family planning’ based on a composite of beliefs about using services if needed.

Trial registration

ISRCTN registry ISRCTN12671153. Retrospectively registered on 17/04/2023.
Disentangling detrimental sand fly-mite interactions in a closed laboratory sand fly colony: implications for vector-borne disease studies and guidelines for overcoming severe mite infestations
Authors: Nzelu Chukwunonso O. , Meneses Claudio , Bowhay Christina , Coutinho-Abreu Iliano V. , Bennett Emily , Bahrami Somayeh , Bonilla Brian , Kamhawi Shaden , Valenzuela Jesus G. , Peters Nathan C.
Published: January 2024

Background

Vector sand fly colonies are a critical component of studies aimed at improving the understanding of the neglected tropical disease leishmaniasis and alleviating its global impact. However, among laboratory-colonized arthropod vectors of infectious diseases, the labor-intensive nature of sand fly rearing coupled with the low number of colonies worldwide has generally discouraged the widespread use of sand flies in laboratory settings. Among the different factors associated with the low productivity of sand fly colonies, mite infestations are a significant factor. Sand fly colonies are prone to infestation by mites, and the physical interactions between sand flies and mites and metabolites have a negative impact on sand fly larval development.

Methods

Mites were collected from sand fly larval rearing pots and morphologically identified using taxonomic keys. Upon identification, they were photographed with a scanning electron microscope. Several mite control measures were adopted in two different laboratories, one at the Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases-National Institutes of Health (Rockville, MD, USA), and the other at the University of Calgary (Calgary, AB, Canada).

Results

The mite species associated with sand fly colonies in the two laboratories were morphologically identified as Tyrophagus sp. and Stratiolaelaps scimitus. While complete eradication of mites in sand fly colonies is considered unrealistic, drastically reducing their population has been associated with higher sand fly productivity.

Conclusions

We report a case of detrimental interaction between sand flies and Tyrophagus sp. and S. scimitus in a closed laboratory sand fly colony, discuss their impact on sand fly production and provide guidelines for limiting the mite population size in a closed laboratory colony leading to improved sand fly yields.

Graphical abstract
Unveiling a classical mutant in the context of the GH3 β-glucosidase family in Neurospora crassa
Authors: Zhang Yuxin , Nada Basant , Baker Scott E. , Evans James E. , Tian Chaoguang , Benz J. Philipp , Tamayo Elisabeth
Published: January 2024

Classical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.