bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis
Authors: Su Xiaochen , Chen Anfa , Teng Menghao , Ji Wenchen , Zhang Yingang 
Published: September 2023

Abstract
Background
Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear.

Methods
A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed.

Results
The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (PSM = 3.04 × 10−2, PWB = 9.58 × 10−3). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (PTWAS = 1.32 × 10−2, PDEG = 2.75 × 10−2) and KIAA1109 (PTWAS = 3.71 × 10−2, PDEG = 4.67 × 10−2). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360).

Conclusion
We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA.
Double posteromedial portals versus single posteromedial portal for arthroscopic management of popliteal cysts
Authors: Ma Rui , Zhu Zheyue , Liu Dan , Wang Kunzheng , Yang Pei 
Published: September 2023

Abstract
Background
As a common disease in orthopedic clinics, popliteal cysts often coexist with intra-articular lesions. Compared with traditional open surgery, arthroscopic treatment of popliteal cysts is less traumatic, and intra-articular lesions can be treated. The ‘one-way valve’ mechanism of the popliteal cyst can be removed by expanding the communication between the articular cavity and the cyst to avoid cyst recurrence. In terms of arthroscopic techniques, the comparison of clinical effects between the double posteromedial portal (DPP) and single posteromedial portal (SPP) has rarely been studied. The purpose of this retrospective study was to compare the clinical effects of DPP and SPP.

Methods
A total of 46 consecutive patients with symptomatic popliteal cysts who underwent arthroscopic treatment were included in this study and followed for approximately 1 year. All patients were divided into two groups according to the arthroscopic portals (DPP group and SPP group). The cyst size, Lysholm score and Rauschening–Lindgren (R–L) grade were evaluated before the operation for all patients, and the intra-articular lesions, operative time and complications were recorded after operation. At the last follow-up, the Lysholm score and R–L grade were recorded, and magnetic resonance imaging was used to evaluate the outcome of the cyst. The clinical data of the two groups was statistically compared and analyzed.

Results
There were no significant differences in preoperative cyst size, Lysholm score or R–L grade between the two groups (P > 0.05). The operation time of the DPP group (67.52 ± 18.23 min) was longer than that of the SPP group (55.95 ± 16.40 min) (P = 0.030), but the recurrence rate of cysts in the DPP group (0%) was obviously lower than that in the SPP group (19.0%) (P = 0.046). There were no significant differences in the Lysholm score, R–L grade or complication rate between the two groups at the last follow-up (P > 0.05).

Conclusion
Arthroscopic treatment of popliteal cysts using double posteromedial portals was a safe and effective surgical method.
Trial registration: ChiCTR, ChiCTR2200060115. Registered 19 May 2022, https://www.chictr.org.cn/showproj.html?proj=133199
ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability
Authors: Mazzucato Monica , Pozza Laura Visonà Dalla , Facchin Paola , Angin Cèline , Agius Francis , Cavero-Carbonell Clara , Corrochano Virginia , Hanusova Katerina , Kirch Kurt , Lambert Deborah , Lucano Caterina , Maiella Sylvie , Panzaru Monica , Rusu Cristina , Weber Stefanie , Zurriaga Oscar , Zvolsky Miroslav , Rath Ana 
Published: September 2023

Abstract
Background
Estimates of rare disease (RD) population impact in terms of number of affected patients and accurate disease definition is hampered by their under-representation in current coding systems. This study tested the use of a specific RD codification system (ORPHAcodes) in five European countries/regions (Czech Republic, Malta, Romania, Spain, Veneto region-Italy) across different data sources over the period January 2019-September 2021.

Results
Overall, 3133 ORPHAcodes were used to describe RD diagnoses, mainly corresponding to the disease/subtype of disease aggregation level of the Orphanet classification (82.2%). More than half of the ORPHAcodes (53.6%) described diseases having a very low prevalence (< 1 case per million), and most commonly captured rare developmental defects during embryogenesis (31.3%) and rare neurological diseases (17.6%). ORPHAcodes described disease entities more precisely than corresponding ICD-10 codes in 83.4% of cases.

Conclusions
ORPHAcodes were found to be a versatile resource for the coding of RD, able to assure easiness of use and inter-country comparability across population and hospital databases. Future research on the impact of ORPHAcoding as to the impact of numbers of RD patients with improved coding in health information systems is needed to inform on the real magnitude of this public health issue.
Consensus-based guidelines for the provision of palliative and end-of-life care for people living with epidermolysis bullosa
Authors: Popenhagen Mark P. , Genovese Paola , Blishen Mo , Rajapakse Dilini , Diem Anja , King Alex , Chan Jennifer , Pellicer Arasa Eduard , Baird Simone , Ferreira da Rocha Anna Carolina , Stitt Gideon , Badger Kellie , Zmazek Vlasta , Ambreen Faiza , Mackenzie Caroline , Price Harper , Roberts Toni , Moore Zena , Patton Declan , Murphy Paul , Mayre-Chilton Kattya 
Published: September 2023

Abstract
Background
Inherited epidermolysis bullosa (EB) is a cluster of rare, genetic skin and mucosal fragility disorders with multi-system and secondary effects, in which blistering and erosions occur in response to friction/mechanical trauma. Considering the incurable and potentially life-limiting nature of the condition and the challenges posed by its symptoms, a palliative approach to EB-related care is necessary. However, knowledge and experience related to the provision of EB palliative care is minimal. Evidence-based, best care guidelines are needed to establish a base of knowledge for practitioners to prevent or ease suffering while improving comfort at all stages of the illness, not just the end of life.

Methods
This consensus guideline (CG) was begun at the request of DEBRA International, an international organization dedicated to improvement of care, research, and dissemination of knowledge for EB patients, and represents the work of an international panel of medical experts in palliative care and EB, people living with EB, and people who provide care for individuals living with EB. Following a rigorous, evidence-based guideline development process, the author panel identified six clinical outcomes based on the results of a survey of people living with EB, carers, and medical experts in the field, as well as an exhaustive and systematic evaluation of literature. Recommendations for the best clinical provision of palliative care for people living with EB for each of the outcomes were reached through panel consensus of the available literature.

Results
This article presents evidence-based recommendations for the provision of palliative healthcare services that establishes a base of knowledge and practice for an interdisciplinary team approach to ease suffering and improve the quality of life for all people living with EB. Any specific differences in the provision of care between EB subtypes are noted.

Conclusions
Because there is yet no cure for EB, this evidence-based CG is a means of optimizing and standardizing the IDT care needed to reduce suffering while improving comfort and overall quality of life for people living with this rare and often devastating condition.
Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population
Authors: Sasaki Yuki , Ishikawa Kosuke , Hatanaka Kanako C. , Oyamada Yumiko , Sakuhara Yusuke , Shimizu Tadashi , Saito Tatsuro , Murao Naoki , Onodera Tomohiro , Miura Takahiro , Maeda Taku , Funayama Emi , Hatanaka Yutaka , Yamamoto Yuhei , Sasaki Satoru 
Published: September 2023

Abstract
Background
Klippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS.

Results
Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1.

Conclusions
The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.
The impact of PECS II blockade in patients undergoing minimally invasive cardiac surgery—a prospective, randomized, controlled, and triple-blinded trial
Authors: Hoerner Elisabeth , Stundner Ottokar , Naegele Felix , Fiala Anna , Bonaros Nikolaos , Mair Peter , Holfeld Johannes , Gasteiger Lukas 
Published: September 2023

Abstract
Background
Classic neuraxial techniques, such as thoracic epidural anesthesia, or alternative approaches like the paravertebral block, are not indicated in cardiac surgery due to increased bleeding risk. To provide satisfactory analgesia without the need for excessive opioid use, novel ultrasound techniques gained popularity and are of growing interest. The pectoralis nerve block II (PECS II) has been shown to provide good postoperative analgesia in modified radical mastectomy and might also be suitable for minimally invasive cardiac surgery.

Methods
In a single center, prospective, triple-blinded, two-group randomized trial, 60 patients undergoing elective, unilateral minimal invasive cardiac surgery will be randomized to receive a PECS II with 30 ml of ropivacaine 0.5% (intervention group) or sodium chloride 0.9% (placebo group). The primary outcome parameter is the overall opioid demand given as intravenous morphine milligram equivalents (MME) during the first 24 h after extubation. Secondary endpoints are the visual analog scale (VAS) 2, 4, 6, 8, 12, and 24 h after extubation, the Overall Benefit of Analgesia Score (OBAS) after 24 h, the interval until extubation, and intensive care unit (ICU) discharge within 24 h, as well as the length of hospital stay (LOS).

Discussion
This prospective randomized, controlled, and triple-blinded trial aims to assess if a PECS II with ropivacaine 0.5% helps to decrease the opioid demand in the first 24 h and increases postoperative pain control after minimally invasive cardiac surgery.

Trial registration
www.clinicaltrialsregister.eu; EudraCT Nr: 2021–005452-11; Lukas Gasteiger MD, November 18, 2021.
Bartonella infections are prevalent in rodents despite efficient immune responses
Authors: Rodríguez-Pastor Ruth , Hasik Adam Z. , Knossow Nadav , Bar-Shira Enav , Shahar Naama , Gutiérrez Ricardo , Zaman Luis , Harrus Shimon , Lenski Richard E. , Barrick Jeffrey E. , Hawlena Hadas 
Published: September 2023

AbstractBackgroundPathogens face strong selection from host immune responses, yet many host populations support pervasive pathogen populations. We investigated this puzzle in a model system ofBartonellaand rodents from Israel’s northwestern Negev Desert. We chose to study this system because, in this region, 75–100% of rodents are infected withBartonellaat any given time, despite an efficient immunological response. In this region,Bartonellaspecies circulate in three rodent species, and we tested the hypothesis that at least one of these hosts exhibits a waning immune response toBartonella, which allows reinfections.MethodsWe inoculated captive animals of all three rodent species with the sameBartonellastrain, and we quantified the bacterial dynamics andBartonella-specific immunoglobulin G antibody kinetics over a period of 139 days after the primary inoculation, and then for 60 days following reinoculation with the same strain.ResultsContrary to our hypothesis, we found a strong, long-lasting immunoglobulin G antibody response, with protective immunological memory in all three rodent species. That response prevented reinfection upon exposure of the rodents to the sameBartonellastrain.ConclusionsThis study constitutes an initial step toward understanding how the interplay between traits ofBartonellaand their hosts influences the epidemiological dynamics of these pathogens in nature.Graphical Abstract
The first report on Hepatozoon canis in dogs and wolves in Poland: clinical and epidemiological features
Authors: Tołkacz Katarzyna , Kretschmer Milena , Nowak Sabina , Mysłajek Robert W. , Alsarraf Mustafa , Wężyk Dagmara , Bajer Anna 
Published: September 2023

Abstract
Background
Canine hepatozoonosis caused by Hepatozoon canis is a common infection in dogs, with frequent case reports from the Mediterranean region and more recently from several Central European countries, such as Hungary and Germany. Despite the high prevalence of H. canis in red foxes, no infections have been reported to date in dogs in Poland. We describe here the first autochthonous cases of H. canis infection in dogs, including their clinical features, and report the prevalence of H. canis in grey wolves from different regions of Poland.

Methods
Thin smears prepared from blood samples collected from dogs were evaluated by microscopic examination. A total of 60 wolves and 47 dogs were tested. Infections were confirmed by PCR and sequencing.

Results
Gamonts of H. canis were found in > 50% of the neutrophils of two dogs and in < 10% of the neutrophils in another five dogs. Molecular typing by PCR sequencing of the 18S ribosomal RNA gene fragment confirmed infections in 11 dogs from different regions of Poland, in 2.7% of dogs attending veterinary practices in central Poland and in 35% of wolves from various geographical regions of Poland. Clinical features manifested mostly in older dogs, and the most common signs were anaemia and apathy. Young dogs usually remained asymptomatic.

Conclusions
This is the first report of H. canis infection in dogs and wolves in Poland. Although the exact vector of the parasite is not known, veterinary practitioners should be aware of this new parasitosis and should consider appropriate diagnostics to confirm/exclude this infection. Further studies are needed to understand the transmission routes of H. canis in domestic and wild canids in Poland.

Graphical Abstract
Revealing the developmental origin and lineage predilection of neural progenitors within human bone marrow via single-cell analysis: implications for regenerative medicine
Authors: Changmeng Zhang , Hongfei Wang , Cheung Martin Chi-Hang , Chan Ying-Shing , Shea Graham Ka-Hon 
Published: September 2023

Abstract
Background
Human bone marrow stromal cells (BMSCs) are an easily accessible and expandable progenitor population with the capacity to generate neural cell types in addition to mesoderm. Lineage tracing studies in transgenic animals have indicated Nestin + BMSCs to be descended from the truncal neural crest. Single-cell analysis provides a means to identify the developmental origin and identity of human BMSC-derived neural progenitors when lineage tracing remains infeasible. This is a prerequisite towards translational application.

Methods
We attained transcriptomic profiles of embryonic long bone, adult human bone marrow, cultured BMSCs and BMSC-derived neurospheres. Integrated scRNAseq analysis was supplemented by characterization of cells during culture expansion and following provision of growth factors and signalling agonists to bias lineage.

Results
Reconstructed pseudotime upon the integrated dataset indicated distinct neural and osteogenic differentiation trajectories. The starting state towards the neural differentiation trajectory consisted of Nestin + /MKI67 + BMSCs, which could also be diverted towards the osteogenic trajectory via a branch point. Nestin + /PDGFRA + BMSCs responded to neurosphere culture conditions to generate a subpopulation of cells with a neuronal phenotype according to marker expression and gene ontogeny analysis that occupied the end state along the neural differentiation trajectory. Reconstructed pseudotime also revealed an upregulation of BMP4 expression during culture of BMSC-neurospheres. This provided the rationale for culture supplementation with the BMP signalling agonist SB4, which directed progenitors to upregulate Pax6 and downregulate Nestin.

Conclusions
This study suggested BMSCs originating from truncal neural crest to be the source of cells within long bone marrow possessing neural differentiation potential. Unravelling the transcriptomic dynamics of BMSC-derived neural progenitors promises to enhance differentiation efficiency and safety towards clinical application in cell therapy and disease modelling.
A bioavailable form of curcumin suppresses cationic host defence peptides cathelicidin and calprotectin in a murine model of collagen-induced arthritis
Authors: Hemshekhar Mahadevappa , Lloyd Dylan , El-Gabalawy Hani , Mookherjee Neeloffer 
Published: September 2023

AbstractCurcumin, a component of the South-Asian spice turmeric, elicits anti-inflammatory functions. We have previously demonstrated that a highly bioavailable formulation of cucurmin, Cureit/Acumin™ (CUR), can suppress disease onset and severity, in a collagen-induced arthritis (CIA) mouse model. In a previous study, we have also shown that the abundance of antimicrobial host defence peptides, specifically cathelicidin (CRAMP) and calprotectin (S100A8 and S100A9), is significantly increased in the joint tissues of CIA mice. Elevated levels of cathelicidin and calprotectin have been associated with the pathogenesis of rheumatoid arthritis. Therefore, in this study, we examined the effect CUR administration on the abundance of cathelicidin and calprotectin in the joints, in a CIA mouse model. Here, we demonstrate that daily oral administration of CUR significantly reduces the elevated levels of CRAMP and calprotectin to baseline in the joints of CIA mice. We also show a linear correlation between the abundance of these peptides in the joints with serum inflammatory cytokines TNFα, IFNγ, and MCP-1. Overall, our results suggest that oral administration of a bioavailable CUR can suppress cathelicidin and calprotectin in the joints and regulate both local (joints) and systemic (serum) inflammation, in inflammatory arthritis.
Dissemination of endometrial cancer MRI staging guidelines among young radiologists: an ESUR Junior Network survey
Authors: Stanzione Arnaldo , Hornia Eduardo Alvarez , Moreira Ana Sofia Linhares , Russo Luca , Andrieu Pamela Causa , Carnelli Carlos , Cuocolo Renato , Brembilla Giorgio , Zawaideh Jeries Paolo ,   for the ESUR Junior Network Committee, Alessandrino Francesco , Bonanno Nathania , Bura Vlad , de Rooij Maarten , Konidari Marianna , Panico Camilla , Palm Viktoria , Pecoraro Martina , Ponsiglione Andrea , Sharaf Doaa E. , Sofia Carmelo , Wu Chen-Jiang 
Published: September 2023

Abstract
Objectives
Imaging guidelines could play an important role in the training of radiologists, but the extent of their adoption in residency programs is unclear. With this survey, the European Society of Urogenital Radiology (ESUR) Junior Network aimed to assess the dissemination of the ESUR guidelines on endometrial cancer MRI staging (EC-ESUR guidelines) among young radiologists.

Methods
An online questionnaire targeted to last year radiology residents and radiologists in the first year of their career was designed. It included 24 questions, structured in 4 sections (i.e., background, general, acquisition protocol, interpretation, and reporting). The survey was active between April and May 2022, accepting answers worldwide. Answers were solicited with a social media campaign and with the support of national scientific societies. Subgroup analysis was performed based on variables such as subspecialty of interest and number of EC-ESUR guidelines consultations using the Wilcoxon rank sum test.

Results
In total, 118 participants completed the questionnaire, of which 94 (80%) were from Europe and 46 (39%) with a special interest in urogenital radiology. Overall, 68 (58%) stated that the guidelines were not part of their residency teaching programs while 32 (27%) had never even consulted the guidelines. Interest in urogenital radiology as a subspecialty and EC-ESUR guidelines consultations were associated with greater confidence in supervising scan acquisition, interpreting, and reporting EC MRI staging exams.

Conclusion
Four years after publication, the adoption of EC-ESUR guidelines in residency programs is heterogeneously low. Despite a possible selection bias, our findings indicate that active promotion of EC-ESUR guidelines is required.

Key points
• The adoption of ESUR guidelines on endometrial cancer in radiology residency programs is heterogeneous.
• Almost one third of respondents stated they had never even consulted the guidelines.
• Confidence toward guidelines was higher in those who were exposed to more endometrial cancer MRI staging scans.
• Reading the guidelines was associated with a greater confidence in protocol acquisition, interpretation, and reporting.
• Active efforts to promote their dissemination are required.