bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of low-dose interferon alpha-2a treatment in Behçet’s Syndrome with refractory vascular or neurological involvement: a case series
Authors: Sun Luxi , Hou Yunxia , Zhang Lifan , Liu JinJing , Li Lu , Wang Zhimian , Yu Xin , Zhang Menghao , Liu Xiaoqing , Zhao Yan , Zheng Wenjie 
Published: July 2022

Objective: The aim of this study was to evaluate the effectiveness and safety of low-dose interferon alpha-2a (IFNα2a) in Behçet’s syndrome (BS) patients with refractory vascular/cardiac or neurological involvement. Methods: In this retrospective cohort study, we consecutively included 25 BS patients with refractory vascular/cardiac ( n = 16) or neurological involvement ( n = 9) who received IFNα2a treatment in our center between June 2018 and September 2021. The low-dose IFNα2a (3 million IU, every other day) was used as an add-on treatment with the continuation of glucocorticoids (GCs) and immunosuppressants. Results: In total, 25 patients (20 males, 5 females) with a mean age of 31.92 ± 9.25 years were included. IFNα2a was administered for BS patients with refractory vascular/cardiac involvement ( n = 16) and neurological involvement ( n = 9). Before the initiation of IFNα2a, patients had insufficient response or intolerance to conventional therapies. After a median follow-up of 23 [interquartile range (IQR), 11–30] months, all patients achieved clinical improvement. The Behçet’s disease Current Activity Form (BDCAF) score improved significantly (5 versus 0, median, p < 0.0001). BS Overall Damage Index (BODI) and vasculitis damage index (VDI) remain stable ( p > 0.05). Decrease in erythrocyte sedimentation rate [ESR; 24 (IQR, 12–43.5) versus 5 (IQR, 2.75–10.5) mm/h, p = 0.0001] and C-reactive protein [CRP; 6.64 (IQR, 3.67–19.82) versus 1.24 (IQR, 0.24–3.12) mg/liter, p < 0.005] was achieved effectively. The median GCs dosage tapered from 26.25 (IQR, 11.88–41.25) to 10.00 (IQR, 7.50–10.63) mg/d, p < 0.0001. Immunosuppressants were also reduced in number ( p < 0.005). No serious adverse events were observed during follow-up. Conclusion: Our study suggests that low-dose IFNα2a, combined with GCs and immunosuppressants, is well-tolerated and effective for BS patients with refractory vascular/cardiac or neurological involvement and has a steroid- and immunosuppressant-sparing effect.
Franksousaite, PbCu(Se6+O4)(OH)2, the Se6+ analogue of linarite, a new mineral from the El Dragón mine, Potosí, Bolivia
Authors: Yang Hexiong , McGlasson James A. , Gibbs Ronald B. , Downs Robert T. 
Published: July 2022

AbstractA new mineral species, franksousaite (IMA2021-096), ideally PbCu(Se6+O4)(OH)2, has been found from the El Dragón mine, Antonio Quijarro Province, Potosí Department, Bolivia. It occurs as short prismatic crystals included in colourless anglesite. Associated minerals are Co-bearing krut'aite–penroseite, chalcomenite, schmiederite, olsacherite, phosgenite, anglesite and cerussite. Franksousaite is blue in transmitted light, transparent with very pale blue streak and has a vitreous lustre. It is brittle and has a Mohs hardness of 2–2½. Cleavage is perfect on {100}. The calculated density is 5.64 g/cm3. An electron microprobe analysis yielded an empirical formula (based on 6 O apfu) of Pb1.02Cu0.98[(Se0.84S0.17)Σ1.01O4)](OH)2, which is simplified to PbCu[(Se,S)O4)](OH)2.Franksousaite is the Se6+ analogue of linarite, PbCu(SO4)(OH)2. It is monoclinic, with space group P21/m and unit-cell parameters a = 9.8208(3), b = 5.7340(2), c = 4.74980(10) Å, β = 102.683(2)°, V = 260.947(13) Å3 and Z = 2. The crystal structure of franksousaite consists of Jahn-Teller-distorted Cu2+O6 square bipyramids, which form chains along b by sharing trans edges across their square planes. The chains are decorated by SeO4 tetrahedra and linked to one another by hydrogen bonds to form layers parallel to (100). These layers are bound together by double layers of PbO8 and SeO4 polyhedra. The PbO8 polyhedron exhibits one-sided coordination typical of Pb2+ with a stereochemically active 6s2 lone-electron-pair. The major structural difference between franksousaite and linarite lies in the <Se–O> vs. <S–O> bond distances (1.615 vs. 1.482 Å), accounting for the larger unit-cell volume for franksousaite. A comparison of Raman spectra for the four minerals in the linarite group (linarite, franksousaite, munakataite and schmiederite) reveals the obvious differences among them, especially in the range from 700 to 1000 cm–1, indicative of the presence or absence of (Se4+O3)2–, (Se6+O4)2–, and/or (SO4)2– groups.
Improving NK cell function in multiple myeloma with NKTR-255, a novel polymer-conjugated human IL-15
Authors: Fernandez Rafael Alonso , Mayoral Jessica Encinas , Pierre-Louis Laetitia , Yao Yao , Xu Yan , Mu Shidai , Martinez-Lopez Joaquin , Primo Daniel , Miyazaki Takahiro , Prabhala Rao , Anderson Kenneth C. , Overwijk Willem W. , Munshi Nikhil C. , Fulciniti Mariateresa 
Published: July 2022

Abstract
Multiple myeloma (MM) is characterized by an immunosuppressive microenvironment that enables tumor development. One of the mechanisms of immune evasion used by MM cells is the inhibition of natural killer (NK) cell effector functions; thus, the restoration of NK cell antitumor activity represents a key goal to increase tumor cell recognition, avoid tumor escape and potentially enhancing the effect of other drugs. In this study, we evaluated the ability of the investigational medicine NKTR-255, an IL-15 receptor agonist, to engage the IL-15 pathway and stimulate NK cells against MM cells. We observed that incubation with NKTR-255 was able to tilt the balance toward an activated phenotype in NK cells isolated from peripheral blood mononuclear cells of patients with MM, with increased expression of activating receptors on the surface of treated NK cells. This resulted in an enhanced degranulation, cytokine release, and anti-tumor cytotoxicity when the NK cells were exposed to both MM cell lines and primary MM cells. We further evaluated the in vivo effect of NKTR-255 in fully humanized immunocompetent mice subcutaneously engrafted with H929 MM cells. Compared with placebo, weekly injection of the mice with NKTR-255 increased the number of circulating NK cells in peripheral blood and delayed tumor growth. Finally, we observed that combination of NKTR-255 with the anti-CD38 antibody, daratumumab, was effective against MM cells in vitro and in vivo. Taken together, our data suggest a significant impact of NKTR-255 in inducing NK cell function against MM cells with important translational implications.
Gradually shifting clinical phenomics in migraine spectrum: a cross-sectional, multicenter study of 5438 patients
Authors: Ran Ye , Yin Ziming , Lian Yajun , Xu Yanmei , Li Yajie , Liu Jiale , Gu Qun , Yan Fanhong , Ge Zhaoli , Lian Yu , Hu Dongmei , Chen Sufen , Wang Yangyang , Wang Xiaolin , Wang Rongfei , Chen Xiaoyan , Liu Jing , Zhang Mingjie , Han Xun , Xie Wei , Yu Zhe , Cao Ya , Li Yingji , Li Ke , Dong Zhao , Yu Shengyuan 
Published: July 2022

Abstract
Background
The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum.

Methods
In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis.

Results
Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree’s accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM.

Conclusions
The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different “predominant regions” that generate attacks.
Exploring the lncRNA localization landscape within the retinal pigment epithelium under normal and stress conditions
Authors: Kaczynski Tadeusz J. , Au Elizabeth D. , Farkas Michael H. 
Published: July 2022

AbstractBackgroundLong noncoding RNAs (lncRNAs) are emerging as a class of genes whose importance has yet to be fully realized. It is becoming clear that the primary function of lncRNAs is to regulate gene expression, and they do so through a variety of mechanisms that are critically tied to their subcellular localization. Although most lncRNAs are poorly understood, mapping lncRNA subcellular localization can provide a foundation for understanding these mechanisms.ResultsHere, we present an initial step toward uncovering the localization landscape of lncRNAs in the human retinal pigment epithelium (RPE) using high throughput RNA-Sequencing (RNA-Seq). To do this, we differentiated human induced pluripotent stem cells (iPSCs) into RPE, isolated RNA from nuclear and cytoplasmic fractions, and performed RNA-Seq on both. Furthermore, we investigated lncRNA localization changes that occur in response to oxidative stress. We discovered that, under normal conditions, most lncRNAs are seen in both the nucleus and the cytoplasm to a similar degree, but of the transcripts that are highly enriched in one compartment, far more are nuclear than cytoplasmic. Interestingly, under oxidative stress conditions, we observed an increase in lncRNA localization in both nuclear and cytoplasmic fractions. In addition, we found that nuclear localization was partially attributable to the presence of previously described nuclear retention motifs, while adenosine to inosine (A-to-I) RNA editing appeared to play a very minimal role.ConclusionsOur findings map lncRNA localization in the RPE and provide two avenues for future research: 1) how lncRNAs function in the RPE, and 2) how one environmental factor, in isolation, may potentially play a role in retinal disease pathogenesis through altered lncRNA localization.
The spatiotemporal regulations of epicatechin biosynthesis under normal flowering and the continuous inflorescence removal treatment in Fagopyrum dibotrys
Authors: Guo Xinwei , Luo Zuliang , Zhang Min , Huang Linfang , Wang Hui , Li Yuting , Qiao Xu , Li Ailian , Wu Bin 
Published: July 2022

Abstract
Background
Flowering is a critical physiological change that interferes with not only biomass yield but also secondary metabolism, such as the biosynthesis of flavonoids, in rhizome/root plants. The continuous inflorescence removal (CIR) treatment is frequently conducted to weaken this effect. Fagopyrum dibotrys (D.Don) H.Hara (Golden buckwheat) is a kind of rhizome medicinal plant rich in flavonoids and is widely used for the treatment of lung diseases. The CIR treatment is usually conducted in F. dibotrys because of its excessive reproductive growth. To uncover the molecular mechanisms, comprehensive analysis was performed using metabolome and transcriptome data obtained from normally bloomed and the CIR treated plants.

Results
Metabolome results demonstrated that in the rhizomes of F. dibotrys, its bioactive compound called epicatechin has higher amount than most of the detected precursors. Compared with the normally bloomed plants, the level of epicatechin in the rhizomes of the CIR group increased by 25% at the withering stage. Based on 96 samples of the control and the CIR groups at 4 flowering stages for 4 tissues, RNA-Seq results revealed a 3 ~ 5 times upregulations of all the key enzyme genes involved in the biosynthesis of epicatechin in both time (from the bud stage to the withering stage) and spatial dimensions (from the top of branch to rhizome) under the CIR treatment compared to normal flowering. Integrated analysis of LC–MS/MS and transcriptome revealed the key roles of several key enzyme genes besides anthocyanidin reductase (ANR). A total of 93 transcription factors were identified to co-expressed with the genes in epicatechin biosynthetic pathway. The flowering activator SQUAMOSA promoter-binding protein like (SPLs) exhibited opposite spatiotemporal expression patterns to that of the epicatechin pathway genes; SPL3 could significantly co-express with all the key enzyme genes rather than the flowering repressor DELLA. Weighted gene co-expression network analysis (WGCNA) further confirmed the correlations among chalcone synthases (CHSs), chalcone isomerases (CHIs), ANRs, SPLs and other transcription factors.

Conclusions
SPL3 might dominantly mediate the effect of normal flowering and the CIR treatment on the biosynthesis of epicatechin in rhizomes mainly through the negative regulations of its key enzyme genes including CHS, CHI and ANR.
Impact of direct-acting antiviral treatment of hepatitis C on the quality of life of adults in Ukraine
Authors: Benade M. , Rosen S. , Antoniak S. , Chasela C. , Stopolianska Y. , Barnard T. , Gandhi M. M. , Ivanchuk I. , Tretiakov V. , Dible J. , Minior T. , Chew K. W. , van der Horst C. , Tsenilova Z. , Sanne I. 
Published: July 2022

Abstract
Background
Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine.

Methods
Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status.

Results
Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9–82.1) at study entry to 89.4 (88.1–90.7) at 24 weeks, role functioning (64.5 [62.3–66.8] to 86.5 [84.9–88.2]), social functioning (74.2 [72.1–76.2] to 84.8 [83.2–86.5]) and bodily pain (70.1 [68.2–72.0] to 89.8 [88.5–91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants.

Conclusion
QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.
Arterioureteral fistula after radical cystectomy and ureterocutaneostomy: two case reports and a systematic literature review
Authors: Jiang Zhiwen , Wang Jian , Cui Jianfeng , Chen Shouzhen , Qu Sifeng , Wang Wenfu , Guo Hu , Shi Benkang , Zhu Yaofeng 
Published: July 2022

Abstract
Background
Arterioureteral fistula (AUF) is a rare, life-threatening condition wherein communication occurs between a ureter and the common, internal, or external iliac artery. The sensitivity of common clinical imaging examination for AUF is low, which leads to a delayed diagnosis and increased mortality. In addition, the increased use of ureteral stents contributes to the growing frequency of AUF.

Case presentation
Our two patients were 74 and 65 years old males respectively. They both had a medical history of bladder cancer and underwent radical cystectomy with ureterocutaneostomy. The patients underwent routine catheter exchange during over 1 year postradical cystectomy and subsequently experienced intermittent gross pulsatile haematuria. After a series of imaging examinations failed to identify the cause, the patients were ultimately diagnosed with AUF and treated with interventional radiotherapy, followed by broad-spectrum antibiotics. Positive effects were found.

Conclusions
The incidence of AUF is increased with the prolongation of survival in patients with related risk factors. This case report aims to highlight early diagnosis and management of AUF to lower the mortality.
Factors associated with delay in seeking care for breast symptoms
Authors: Soh Jien Yen , Yahya Maya Mazuwin , Bachok Norsa’adah , Wan Zain Wan Zainira , Wong Michael Pak-Kai , Zakaria Zaidi , Hashim Isa Merican Siti Rahmah , Md Hashim Mohd Nizam , Wan Mokhter Wan Mokhzani , Ramely Rosnelifaizur , Zakaria Andee Dzulkarnaen , Mohamad Ikhwan Sani 
Published: July 2022

AbstractBackgroundBreast cancer is the most common cancer in women worldwide. Early detection and intervention are associated with better prognosis and survival. The study aim was to investigate the factors associated with delayed presentation among women with breast symptoms.MethodsAfter ethics approval, a cross-sectional study was conducted from January to October 2020 in women with new breast cancer symptoms at their first visit to our clinic. The “Delayed Presentation” questionnaires in the Malay language were used and distributed among the participants. Demographic data and presentation time were recorded. Presentation time was defined as the duration of symptoms prior to visiting any health care facilities. Respondents with presentation times > 90 days comprised the delayed group. The potential factors associated with the delayed presentation were analyzed using cross-tabulation and multiple logistic regression.ResultsThere were 106 respondents to the questionnaire, with a mean age of 34.0 (SD: 11.2) years, and 73.6% (n = 78) were < 39 years old. A total of 35.8% (n = 38) visited the local government clinic first and only 28.3% (n = 30) came to the BestARi clinic directly. The reasons for presentation were a palpable breast lump on breast self-examination (75.5%, n = 80), mastalgia (15.1%, n = 16), nipple discharge (5.7%, n = 6), skin changes (0.9%, n = 1), and others (2.8%, n = 3). Among the respondents, 10.4% (n = 11) had alternative treatments prior to presentation to a hospital. The mean presentation time was 98.9 (SD: 323.7) days. Most of the participants (61.3%, n = 65) presented to us within 1 month. The delayed presentation group accounted for 19.8% (n = 21) of the respondents. The factor that was significantly associated with delayed presentation was the participants’ perception of symptoms as not dangerous (adjusted OR 3.05, 95% CI 1.11, 8.38).ConclusionsThe percentage of delayed presentations among our patients was lower than the percentage reported in a previous study. Interpretation of a symptom as harmless by the respondent was the only factor significantly associated with delayed presentation.
Peer evaluation and feedback for invasive medical procedures: a systematic review
Authors: Thai Theresa , Louden Diana K. N. , Adamson Rosemary , Dominitz Jason A. , Doll Jacob A. 
Published: July 2022

Abstract
Background
There is significant variability in the performance and outcomes of invasive medical procedures such as percutaneous coronary intervention, endoscopy, and bronchoscopy. Peer evaluation is a common mechanism for assessment of clinician performance and care quality, and may be ideally suited for the evaluation of medical procedures. We therefore sought to perform a systematic review to identify and characterize peer evaluation tools for practicing clinicians, assess evidence supporting the validity of peer evaluation, and describe best practices of peer evaluation programs across multiple invasive medical procedures.

Methods
A systematic search of Medline and Embase (through September 7, 2021) was conducted to identify studies of peer evaluation and feedback relating to procedures in the field of internal medicine and related subspecialties. The methodological quality of the studies was assessed. Data were extracted on peer evaluation methods, feedback structures, and the validity and reproducibility of peer evaluations, including inter-observer agreement and associations with other quality measures when available.

Results
Of 2,135 retrieved references, 32 studies met inclusion criteria. Of these, 21 were from the field of gastroenterology, 5 from cardiology, 3 from pulmonology, and 3 from interventional radiology. Overall, 22 studies described the development or testing of peer scoring systems and 18 reported inter-observer agreement, which was good or excellent in all but 2 studies. Only 4 studies, all from gastroenterology, tested the association of scoring systems with other quality measures, and no studies tested the impact of peer evaluation on patient outcomes. Best practices included standardized scoring systems, prospective criteria for case selection, and collaborative and non-judgmental review.

Conclusions
Peer evaluation of invasive medical procedures is feasible and generally demonstrates good or excellent inter-observer agreement when performed with structured tools. Our review identifies common elements of successful interventions across specialties. However, there is limited evidence that peer-evaluated performance is linked to other quality measures or that feedback to clinicians improves patient care or outcomes. Additional research is needed to develop and test peer evaluation and feedback interventions.