bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundS. 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.ResultsTwo 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.ConclusionThe 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

AbstractIn 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

AbstractR-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

AbstractHaploinsufficiency 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundHereditary 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.ResultsA 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.ConclusionsIntoMed® 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

Abstract
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

Abstract
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.