bluuebunny/crossref_metadata_2025_split huggingface dataset:
Core Outcome Measures in Chronic Rhinosinusitis With Nasal Polyps: In Practice and Research
Authors: Abdulghany Alaaeldein , Surda Pavol , Hopkins Claire 
Published: February 2023

Heterogeneity in outcomes used in clinical trials prevents meta-analysis and contributes to research waste. Core outcome sets aim to address this by defining a small number of essential outcomes that should be measured in all effectiveness trials. Adoption in routine clinical practice can further improve outcomes for patients. There has been a rapid growth in therapeutic options available for patients with chronic rhinosinusitis with nasal polyps, but difficulty comparing results leads to uncertainty into optimum management, and there is a need to define a core outcome set. We consider whether work already undertaken needs to be modified for patients with nasal polyps. We recommend that a core outcome set should include assessment of disease specific quality of life, nasal polyp score, evaluation of sense of smell, alongside need for OCS and surgical treatment and complications from the disease or treatment. Further work is required to achieve international consensus regarding the choice of nasal polyp scoring system.
The Nasal Innate Immune Proteome After Saline Irrigation: A Pilot Study in Healthy Individuals
Authors: Harcourt-Smith Emily A. , Krstic Emerson T. , Soekov-Pearce Belinda J. , Colella Alex D. , Chegeni Nusha , Chataway Timothy K. , Woods Charmaine M. , Aliakbari Kamelya , Carney A. Simon 
Published: February 2023

Background Previous research has shown diminished nasal immune function following nasal saline irrigation (NSI), returning to baseline at 6 hours. The aim of this study was to examine the immune nasal proteome before and after 14 days of nasal irrigation. Methods Seventeen healthy volunteers received either isotonic (IsoSal) or low salt (LowNa) NSI. Nasal secretions were collected before and 30 min after NSI at baseline and again after 14 days. Specimens were analyzed using mass spectrometry to detect proteins of relevance to nasal immune function. Results One thousand eight hundred and sixty-five proteins were identified with significant changes in 71 proteins, of which 23 were identified as part of the innate immune system. Baseline analysis demonstrated an increase of 9 innate proteins after NSI, most after IsoSal. After 14 days, a greater increase in innate peptides was present, with most now in the LowNa group. When NSI solutions were compared, a significant increase in 4 innate proteins, including a 211% in lysozyme, was detected in the LowNa group. Conclusion LowNa NSI demonstrates evidence of improving the innate immune secretions, especially lysozyme, in healthy volunteers.
Defining Expectations for Infants With Hypoplastic Left Heart Syndrome Who Survive Initial Surgical Palliation
Authors: Greenberg Jason W. , Zafar Farhan , Winlaw David S. , Tweddell James S. , Lehenbauer David G. , Cnota James F. , Heydarian Haleh C. , Morales David L. S. 
Published: February 2023

Background Overall one-year non-mortality outcomes for surgically palliated hypoplastic left heart syndrome (HLHS) patients remain understudied. Using the metric Days Alive and Outside of Hospital (DAOH), the present study sought to characterize expectations for surgically palliated patients’ first year of life. Methods The Pediatric Health Information System database was used to identify by ICD-10 code all HLHS patients who underwent surgical palliation (Norwood/hybrid and/or heart transplantation [HTx]) during their index neonatal admission and were successfully discharged alive (n  =  2227) and for whom one-year DAOH could be calculated. DAOH quartiles were used to group patients for analysis. Results Median one-year DAOH was 304 (interquartile range [IQR] 250-327), including a median index admission length of stay of 43 days (IQR 28-77). Patients required a median 2 (IQR 1-3) readmissions, each spanning 9 days (IQR 4-20). One-year readmission mortality or hospice discharge occurred in 6% of patients. Patients with lower-quartile DAOH had a median DAOH of 187 (IQR 124-226), whereas upper-quartile DAOH patients had a median DAOH of 335 (IQR 331-340) ( P < .001). Readmission mortality/hospice-discharge rates were 14% and 1%, respectively ( P < .01). On multivariable analysis, factors independently associated with lower-quartile DAOH included interstage hospitalization (odds ratio [OR] 44.78 [95% confidence interval [CI] 25.1-80.2]), index-admission HTx (8.73 [4.66-16.3]), preterm birth (1.97 [1.34-2.90]), chromosomal abnormality (1.85 [1.26-2.73]), age >7 days at surgery (1.50 [1.14-1.99]), and non-white race/ethnicity (1.33 [1.01-1.75]). Conclusions In the current era, surgically palliated HLHS infants spend approximately 10 months alive and outside of the hospital, although outcomes are highly variable. Knowledge of the factors associated with lower DAOH can inform expectations and guide management decisions.
Safety and Efficacy of Right Axillary Thoracotomy for Repair of Congenital Heart Defects in Children
Authors: Said Sameh M , Greathouse Kristin C , McCarthy Christina M , Brown Nicholas , Kumar Sacha , Salem Mahmoud I , Kloesel Benjamin , Sainathan Sandeep 
Published: February 2023

Background Minimally invasive repair of congenital heart defects in children has not gained wide popularity yet compared to minimally invasive approaches in adults. We sought to review our experience with this approach in children. Methods This study included a total of 37 children (24 girls, 64.9%) with a mean age of 6.5 ± 5.1 years, who underwent vertical axillary right minithoracotomy for repair of a variety of congenital heart defects between May 2020 and June 2022. Results The mean weight of these children was 25.66 ± 18.3 kg. Trisomy 21 syndrome was present in 3 patients (8.1%). The most common congenital heart defects that were repaired via this approach were atrial septal defects (secundum in 11 patients, 29.7%; primum in 5, 13.5%; and unroofed coronary sinus in 1, 2.7%). Twelve patients (32.4%) underwent repair of partial anomalous pulmonary venous connections with or without sinus venosus defects, while 4 patients (10.8%) underwent closure of membranous ventricular septal defects. Mitral valve repair, resection of cor triatriatum dexter, epicardial pacemaker placement, and myxoma resection occurred in 1 patient (2.7%) each. No early mortality or reoperations. All patients were extubated in the operating room, and the mean length of hospital stay was 3.3 ± 2.04 days. Follow-up was complete (mean 7 ± 5 months). No late mortality or reoperations. One patient required epicardial pacemaker placement due to sinus node dysfunction 5 months after surgery. Conclusions Vertical axillary right thoracotomy is a cosmetically superior approach that is safe and effective for repair of a variety of congenital heart defects in children.
Could recurrent painful ophthalmoplegic neuropathy be caused by a neurovascular conflict?: A case report
Authors: Alstadhaug Karl Bjørnar , Bakkejord Grete , Bø Hans Kristian 
Published: February 2023

Objective: Describe and discuss a typical case with recurrent painful ophthalmoplegic neuropathy (RPON), and demonstrate a likely extrinsic compression of the sixth cranial nerve by a vascular loop. Background: RPON is a rare, but well-known entity, characterized by attacks of ophthalmoplegia associated with ipsilateral headache. The etiology is unknown, but a neurovascular conflict (NVC) has been suggested as a cause. Method: A 62-year-old woman presented in the emergency department with a horizontal diplopia that developed a few hours after the onset of a left temporal headache. In the past she had presented to the clinic with the same problem several times. She had been thoroughly examined, but no cause had been found. The symptoms had resolved by themselves. In addition to a classic finding in RPON, gadolinium enhancement and thickening of a cranial nerve, the new MRI scanning detected an NVC. Herein we discuss the relevance of this finding. Conclusion: A neurovascular conflict causing inflammatory demyelination of a single cranial nerve and relapsing remitting painful ophthalmoplegic neuropathy is an alluring idea. However, it is hard to conceive theoretically, and more reported cases with compelling data are needed to give credibility to such an idea.
Pegcetacoplan controls hemolysis in complement inhibitor–naive patients with paroxysmal nocturnal hemoglobinuria
Authors: Wong Raymond Siu Ming , Navarro-Cabrera Juan Ramon , Comia Narcisa Sonia , Goh Yeow Tee , Idrobo Henry , Kongkabpan Daolada , Gómez-Almaguer David , Al-Adhami Mohammed , Ajayi Temitayo , Alvarenga Paulo , Savage Jessica , Deschatelets Pascal , Francois Cedric , Grossi Federico , Dumagay Teresita 
Published: February 2023

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response or intolerance to a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for ≥3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate the efficacy and safety of pegcetacoplan vs control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor–naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomly assigned and stratified based on their number of transfusions (&lt;4 or ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary end points were hemoglobin stabilization (avoidance of &gt;1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n = 35) or control (n = 18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P &lt; .0001) and change from baseline in LDH (least square mean change: pegcetacoplan, −1870.5 U/L; control, −400.1 U/L; difference, −1470.4 U/L; 95% CI, −2113.4 to −827.3; P &lt; .0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor–naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04085601.
Classification and genetics of pediatric B-other acute lymphoblastic leukemia by targeted RNA sequencing
Authors: Migita Natacha Azussa , Jotta Patrícia Yoshioka , Nascimento Natália Paiva do , Vasconcelos Victor Sande , Centoducatte Gabriel Lopes , Massirer Katlin Brauer , Azevedo Amilcar Cardoso de , Brandalise Silvia Regina , Yunes José Andrés 
Published: February 2023

Abstract
Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify the novel subgroups of ALL in 144 B-other and 40 “classical” ALL samples. The classical TCF3-PBX1, ETV6-RUNX1, KMT2A-rearranged, and BCR-ABL1, and novel P2RY8-CRLF2, ABL-, JAK2-, ZNF384-, MEF2D-, and NUTM1-fusions were easily identified by fusion transcript analysis. IGH-CRLF2 and IGH-EPOR were found by abnormally high levels of expression of CRLF2 or EPOR. DUX4-rearranged was identified by the unusual expression of DUX4 genes and an alternative exon of ERG, or by clustering analysis of gene expression. PAX5-driven ALL, including fusions, intragenic amplifications, and mutations were identified by single-nucleotide variant analysis and manual inspection using the IGV software. Exon junction analysis allowed detection of some intragenic ERG and IKZF1 deletions. CRLF2-high associated with initial white blood cell (WBC) counts of ≥50 × 103/μL and GATA3 risk alleles (rs3781093 and rs3824662), whereas ABL/JAK2/EPOR-fusions associated with high WBC counts, National Cancer Institute’s high-risk classification, and IKZF1del. ZNF384-fusions associated with CALLA-negativity and NUTM1-fusions in infants. In conclusion, targeted RNA sequencing further classified 66.7% (96 of 144) B-other ALL cases. All BCP-ALL subgroups, except for iAMP21, hyperdiploid and hypodiploid cases, were identified. Curiously, we observed higher frequencies of females within B-rest ALLs and males in PAX5-driven cases.
Can endocan serve as a molecular “hepatostat” in liver regeneration?
Authors: Yazici Sinan Efe , Gedik Mustafa Emre , Leblebici Can Berk , Kosemehmetoglu Kemal , Gunaydin Gurcan , Dogrul Ahmet Bulent 
Published: February 2023

Abstract
Background
Intriguingly, liver regeneration after injury does not induce uncontrolled growth and the underlying mechanisms of such a “hepatostat” are still not clear. Endocan, a proteoglycan, was implicated in liver regeneration. It can support the function of hepatocyte growth factor/scatter factor in tissue repair after injury. Endostatin, a 20 kDa C-terminal fragment of collagen XVIII, may modulate the cessation of liver regeneration. eEF2K, a protein kinase that regulates protein synthesis, can regulate angiogenesis. Thus, we investigated the role of endocan, endostatin and eEF2K during normal liver regeneration.

Methods
Serum samples and regenerating remnant liver tissues were obtained on various days after partial hepatectomy in rats. mRNA expression levels of Vegf and Pcna were analyzed in addition to immunohistochemical evaluations. Liver tissue protein levels of endostatin, endocan and p-eEF2K/eEF2K were determined with Western blot. Serum levels of endostatin and endocan were assessed with ELISA.

Results
Pcna expression level in residual liver tissues peaked on day-1, while Vegf expression reached its highest level on days 1–3 after partial hepatectomy (70%). Endocan activity declined gradually on days 1–7. The decrease in liver endocan expression was accompanied by an increase in serum endocan levels. Partial hepatectomy induced a rapid increase in liver endostatin levels. Following its surge on day-1, endostatin expression gradually declined, which was accompanied by a peak in serum endostatin. Finally, partial hepatectomy was shown to regulate eEF2K; thus, increasing protein translation.

Conclusions
We revealed possible mechanistic insights into liver regeneration by examining the associations of Pcna, Vegf, endocan, endostatin, eEF2K with hepatic regeneration after partial hepatectomy. Indeed, endocan might serve as a useful biomarker to monitor clinical prognosis in a plethora of conditions such as recovery of donor’s remaining liver after living-donor liver transplant. Whether endocan might represent a strategy to optimize liver regeneration when given therapeutically needs to be investigated in future studies.
Oxidative stress and epigenetics in ocular vascular aging: an updated review
Authors: Zhao Bowen , Zhu Lijia , Ye Meng , Lou Xiaotong , Mou Qianxue , Hu Yuanyuan , Zhang Hong , Zhao Yin 
Published: February 2023

AbstractVascular aging is an inevitable process with advancing age, which plays a crucial role in the pathogenesis of cardiovascular and microvascular diseases. Diabetic retinopathy (DR) and age-related macular degeneration (AMD), characterized by microvascular dysfunction, are the common causes of irreversible blindness worldwide, however there is still a lack of effective therapeutic strategies for rescuing the visual function. In order to develop novel treatments, it is essential to illuminate the pathological mechanisms underlying the vascular aging during DR and AMD progression. In this review, we have summarized the recent discoveries of the effects of oxidative stress and epigenetics on microvascular degeneration, which could provide potential therapeutic targets for DR and AMD.
Clinical evaluation of super-responders vs. non-responders to CGRP(-receptor) monoclonal antibodies: a real-world experience
Authors: Raffaelli Bianca , Fitzek Mira , Overeem Lucas H. , Storch Elisabeth , Terhart Maria , Reuter Uwe 
Published: February 2023

Abstract
Background
Clinical trials and real-world studies revealed a spectrum of response to CGRP(-receptor) monoclonal antibodies (mAbs) in migraine prophylaxis, ranging from no effect at all to total migraine freedom. In this study, we aimed to compare clinical characteristics between super-responders (SR) and non-responders (NR) to CGRP(-receptor) mAbs.

Methods
We performed a retrospective cohort study at the Headache Center, Charité – Universitätsmedizin Berlin. The definition of super-response was a ≥ 75% reduction in monthly headache days (MHD) in the third month after treatment initiation compared to the month prior to treatment begin (baseline). Non-response was defined as ≤ 25% reduction in MHD after three months of treatment with a CGRP-receptor mAb and subsequent three months of treatment with CGRP mAb, or vice versa. We collected demographic data, migraine disease characteristics, migraine symptoms during the attacks in both study groups (SR/NR) as well as the general medical history. SR and NR were compared using Chi-square test for categorical variables, and t-test for continuous variables.

Results
Between November 2018 and June 2022, n = 260 patients with migraine received preventive treatment with CGRP(-receptor) mAbs and provided complete headache documentation for the baseline phase and the third treatment month. Among those, we identified n = 29 SR (11%) and n = 26 NR (10%). SR reported more often especially vomiting (SR n = 12/25, 48% vs. NR n = 4/22, 18%; p = 0.031) and typical migraine characteristics such as unilateral localization, pulsating character, photophobia and nausea. A subjective good response to triptans was significantly higher in SR (n = 26/29, 90%) than in NR (n = 15/25, 60%, p = 0.010). NR suffered more frequently from chronic migraine (NR n = 24/26, 92% vs. SR n = 15/29, 52%; p = 0.001), medication overuse headache (NR n = 14/24, 58% versus SR n = 8/29, 28%; p = 0.024), and concomitant depression (NR n = 17/26, 65% vs. SR n = 8/29, 28%; p = 0.005).

Conclusion
Several clinical parameters differ between SR and NR to prophylactic CGRP(-R) mAbs. A thorough clinical evaluation prior to treatment initiation might help to achieve a more personalized management in patients with migraine.
IRE1α arm of unfolded protein response in muscle-specific TGF-β signaling-mediated regulation of muscle cell immunological properties
Authors: Xiao Jiangwei , Huang Jingwen , Jian Xiaoting , Wang Han , Lan Haiqiang , Liao Zhaohong , Gu Ruicai , Hu Jijie , Liao Hua 
Published: February 2023

AbstractEndoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are involved in various muscle pathological states. The IRE1α arm of UPR can affect immunological properties of myofiber through restraining p38 mitogen-activated protein kinases (MAPK) activation under inflammatory milieu. However, the relevant pathway molecules regulating the initiation of the IRE1α arm in myofiber remain unclear. In this work, expression of transforming growth factor-beta (TGF-β) and TGF-β receptor II (TGF-βr2), and UPR pathway activation were examined in cardiotoxin (CTX)-damaged mouse muscle, which revealed the activation of TGF-β signaling and UPR in CTX-damaged muscle and in regenerating myofibers. Using control or transgenic mice with TGF-βr2 deleted in skeletal muscle (SM TGF-βr2−/−) and the derived primary differentiating myogenic precursor cells (MPCs) treated with/without ERS activator or inhibitor, IRE1α pathway inhibitor, or TGF-β signaling activator, this study further revealed an essential role of intrinsic TGF-β signaling in regulating muscle cell to express inflammation-related molecules including H-2Kb, H2-Eα, TLR3, and special myokines. TGF-β signaling prompted UPR IRE1α arm and restrained p38 MAPK activation in myofiber under inflammatory milieu. This study uncovers a previously unrecognized function of TGF-β signaling acting as an upstream factor controlling myofiber immune capacities in the inflamed state through the UPR–IRE1α–p38 MAPK pathway.
The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells
Authors: Duan Shouxing , Jiang Xuewu , Li Jianhong , Fu Maxian , Li Zhuo , Cheng Yiyi , Zhuang Yangmu , Yang Ming , Xiao Wenfeng , Ping Hongyan , Xie Yao , Xie Xiaojun , Zhang Xuan 
Published: February 2023

Abstract
Background
Testicular hypoplasia can affect the sexual and reproductive ability in adulthood, and even increase the risk of cancer. Abnormal development of the gubernaculum is one of the important factors of testicular hypoplasia. Therefore, a study of the structure and function of the gubernaculum is an important but neglected new breakthrough point for investigating the normal/abnormal development of the testis. Previous findings showed that Insulin like factor 3 (INSL3) is a key factor regulating the growth of gubernaculum, however, the mechanism by which INSL3 acts on the gubernaculum remains unknown. Therefore, we probed the mechanism associated with INSL3-induced the proliferation, migration, and apoptosis of gubernacular cells in mice.

Methods
A culture cell model of neonatal mice gubernaculum is established by INSL3 intervention. We blocked PLC/PKC signaling pathway with U73122 pretreat to investigate the role of the PLC/PKC signaling pathway. The changes of cell proliferation, migration, and apoptosis were detected by molecular biological methods. In addition, the levels of PCNA and F-action were detected by immunofluorescence and western blotting.

Results
We found that INSL3 can promote the proliferation and migration of gubernacular cells and inhibit their apoptosis, meanwhile, INSL3 significantly up-regulated PLC/PKC protein phosphorylation. However, treatment with the PLC/PKC signaling pathway inhibitor U73122 significantly inhibited these effects of INSL3. Besides, we found that INSL3 could up-regulate the protein expression level of PCNA and F-actin, while the PCNA and F-actin expression was significantly weakened after U73122 pretreatment.

Conclusions
This research revealed that INSL3 binding to RXFP2 may up-regulate the expression levels of PCNA and F-actin by activating the PLC/PKC signaling pathway to promote the proliferation and migration of gubernacular cells. It suggests that the RXFP2-PLC/PKC axis may serve as a novel molecular mechanism by which INSL3 regulates growth of the gubernaculum.