bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics
Authors: Kwon Oh Chan , Choi Wonho , Ahn Soo Min , Oh Ji Seon , Hong Seokchan , Lee Chang-Keun , Yoo Bin , Park Min-Chan , Kim Yong-Gil 
Published: April 2024

Abstract
Background
To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA).

Methods
This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient’s global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi.

Results
Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline.

Conclusions
Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.
Electronic Patient-Reported Outcome–Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial
Authors: Dai Wei , Wang Yaqin , Liao Jia , Wei Xing , Dai Zhen , Xu Wei , Liu Yangjun , Wang Xin Shelley , Pompili Cecilia , Yu Hongfan , Pu Yang , Zhao Yuqian , Cao Bangrong , Wang Qifeng , Feng Wenhong , Zhang Yuanqiang , Liu Fang , Deng Yuanle , Zhou Jin , Li Juan , Xie Shaohua , Xiang Run , Wang Xiang , Tian Bo , Yang Xiaozun , Hu Bin , Liu Xiaoqin , Xie Tianpeng , Yang Xiaojun , Zhuang Xiang , Qiao Guibin , Li Qiang , Shi Qiuling 
Published: April 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported superior symptom control of electronic patient-reported outcome (ePRO)–based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, –0.86 [95% CI, –1.32 to –0.39]) and affective interference (estimate, –0.70 [95% CI, –1.14 to –0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.
Two Cases of Adrenal Cysts Lined by Thyroid Follicular Epithelium: Addressing Cellular Origin and Malignancy Concerns
Authors: Kanzawa Maki , Kanda Tomonori , Fukuoka Hidenori , Shigemura Katsumi , Nakamura Yasuhiro , Itoh Tomoo 
Published: April 2024

Abstract
Adrenal cysts lined by thyroid follicular epithelium are rare, with only 14 reported cases of “ectopic thyroid tissue” to date. While the primary consideration for differential diagnosis is thyroid carcinoma metastasis, exclusion of metastases is determined based on the absence of a primary thyroid lesion, serological euthyroidism, lack of thyroglobulin elevation, and absence of epithelial atypia. Herein, we report 2 cases of adrenal cysts lined by thyroid follicular epithelium. Case 1 was a 60-year-old woman with a right adrenal cyst. Case 2 was a 51-year-old man with a left adrenal cyst. Over time, both cysts became larger, necessitating an adrenalectomy. Cystic epithelia were lined with thyroid follicular epithelium, exhibiting moderate atypia. Human bone marrow endothelial cell marker-1 and galectin-3 were focally positive; CK19 was positive in Case 1, and all 3 markers were positive in Case 2, previously reported as an immunophenotype of thyroid carcinoma. CD56 expression was positive in both cases. Targeted next-generation sequencing revealed several low-frequency mutations; however, no major driver alterations for thyroid cancer were detected. Adrenal cysts can be lined by thyroid follicular epithelium. Challenges arise in determining the malignant or benign nature of adrenal cysts.
Effect of Vitamin D Supplementation on Muscle Function in Patients With I131-Induced Hypothyroidism: A Pilot Randomized Trial
Authors: Maneewan Sureephan , Manosroi Worapaka , Jesadaporn Panas , Phimphilai Mattabhorn , Tipduangta Pratchaya 
Published: April 2024

AbstractBackgroundThere is a lack of data regarding the effect of vitamin D supplements in patients with I131-induced hypothyroidism. The primary aim of this study was to investigate the effect of vitamin D supplements on muscle function, and the secondary aim was to observe the effect on body composition, insulin resistance, and quality of life (QOL) in patients with I131-induced hypothyroidism.MethodsIn this pilot randomized placebo-controlled trial, patients with I131-induced hypothyroidism on a stable dose of levothyroxine were enrolled and allocated into 2 groups to receive oral vitamin D 20 000 IU weekly or placebo for 24 weeks. Baseline biochemical values, body composition, handgrip strength, the 5 times sit-to-stand test (5TSTS), homeostatic model assessment for insulin resistance (HOMA-IR), and QOL were measured before intervention and after 3 and 6 months in both groups. Mixed model regression analysis was used to compare the outcomes between the 2 groups. Significance was set at P value of &lt; .05.ResultsThere were 20 participants in each group. The time taken for 5TSTS in the vitamin D group was significantly lower than the placebo group at 3 (P = .032) and 6 months (P = .006). Other outcomes, including handgrip strength, body composition, HOMA-IR, and QOL, showed no significant difference between the 2 groups.ConclusionA supplement of vitamin D2 at 20 000 IU per week for 24 weeks could help improve performance in 5TSTS in patients with I131-induced hypothyroidism.
A Novel Rat Model of Venous Hypertensive Myelopathy Produced by Arteriovenous Bypass Plus Venous Stenosis
Authors: Wang Yinqing , Yang Chengbin , Wang Jiachen , Wei Mengping , Xu Qing , Wang Zhanjing , Tu Tianqi , Fan Yuxiang , Song Zihao , Duan Wanru , Chen Chunmei , Zhang Hongqi , Ma Yongjie 
Published: April 2024

BACKGROUND AND OBJECTIVES:
Venous hypertensive myelopathy (VHM), mainly induced by the spinal dural arteriovenous fistula, is a congestive spinal cord injury that currently has no appropriate animal model available in preclinical research.

METHODS:
Sprague Dawley rats (280-320 g) were used. The rats were divided into 3 groups: (1) Group 1, which underwent renal artery-dorsal spinal venous bypass (AVB group); (2) Group 2, which underwent renal artery-dorsal spinal venous bypass and drainage vein stenosis (AVB/VS group); and (3) Control group, with T13 dorsal vein ligation. The success of the model was assessed using Doppler ultrasound and 7.0-T magnetic resonance imaging. Transmission electron microscopy, histochemistry, proteomics, and western blot analysis were used to evaluate ultrastructural, pathological, and molecular features in the spinal cord and cerebrospinal fluid (CSF).

RESULTS:
The success rate of the arteriovenous bypass was 100% at 5 days and 83% at 2 weeks. The locomotor assessment showed decreased lower extremity strength in the AVB/VS group (P = .0067), whereas unremarkable changes were found in the AVB and Control groups. Histochemical staining suggested a 2-fold expansion of the dorsal spinal vein in the AVB/VS group, which was lower than that in the AVB group (P < .05); however, the former displayed greater myelin and neuronal damage (P < .05) and slight dilatation of the central canal (P > .05). Proteomics analysis revealed that the complement and coagulation cascade pathways were upregulated in the CSF of AVB/VS rats, whereas the C3 level was elevated both in the CSF and bilateral spinal cord. Furthermore, overexpression of C3, ITGB2, and CD9 in the spinal cord was confirmed by immunoblotting.

CONCLUSION:
These findings suggest that the AVB/VS model can effectively mimic the clinical and molecular characteristics of VHM. Furthermore, they suggest that impaired deep intramedullary venous drainage is the key reason for the VHM.
Piezo1 and Piezo2 collectively regulate jawbone development
Authors: Nie Xuguang , Abbasi Yasaman , Chung Man-Kyo 
Published: April 2024

ABSTRACT
Piezo1 and Piezo2 are recently reported mechanosensory ion channels that transduce mechanical stimuli from the environment into intracellular biochemical signals in various tissues and organ systems. Here, we show that Piezo1 and Piezo2 display a robust expression during jawbone development. Deletion of Piezo1 in neural crest cells causes jawbone malformations in a small but significant number of mice. We further demonstrate that disruption of Piezo1 and Piezo2 in neural crest cells causes more striking defects in jawbone development than any single knockout, suggesting essential but partially redundant roles of Piezo1 and Piezo2. In addition, we observe defects in other neural crest derivatives such as malformation of the vascular smooth muscle in double knockout mice. Moreover, TUNEL examinations reveal excessive cell death in osteogenic cells of the maxillary and mandibular arches of the double knockout mice, suggesting that Piezo1 and Piezo2 together regulate cell survival during jawbone development. We further demonstrate that Yoda1, a Piezo1 agonist, promotes mineralization in the mandibular arches. Altogether, these data firmly establish that Piezo channels play important roles in regulating jawbone formation and maintenance.
Blood Flow-Restricted Training and Time Trial Performance: A Cohort Study of World-Class Rowers
Authors: THOMPSON KYLE M. A. , PETHICK WENDY A. , CLARKE JORDAN , WINEGARDEN ANNEKE , JOHNSON ELIZABETH , COATES ALEXANDRA M. , STELLINGWERFF TRENT , BURR JAMIE F. 
Published: April 2024

ABSTRACTIntroductionThis study aimed to explore the potential impact of incorporating blood flow restriction (BFR) training within a training block characterized by minimal high-intensity work on 2000-m rowing ergometer time trial (TT) performance in elite/world-class rowers. Physiological markers often associated with endurance performance (maximal aerobic capacity, V̇O2max; blood lactate thresholds and hemoglobin mass, Hbmass) were measured to determine whether changes are related to an improvement in performance.MethodsUsing a quasi-experimental, observational study design (no control group), 2000-m TT performance, V̇O2max, submaximal work rates eliciting blood lactate concentrations of ~2 and ~4 mmol·L−1, and Hbmasswere measured before and after 4 wk of noncompetitive season training, which included BFR rowing. BFR training consisted of 11 sessions of 2 × 10 min of BFR rowing at a workload equating to blood lactate concentrations of ~2 mmol·L−1. Pairedt-tests were used to compare pre-/postvalues, and Pearson correlation was used to examine whether physiological changes were associated with changes to TT performance.ResultsTT performance improved in both female (1.09% ± 1.2%, ~4.6 ± 5.2 s;P< 0.01) and male (1.17% ± 0.48%, ~4.5 ± 1.9 s;P< 0.001) athletes. V̇O2maxincreased in female rowers only (P< 0.01), but both sexes had an increase in work rates eliciting blood lactate concentrations of 2 mmol·L−1(female: 184 ± 16 to 195 ± 15 W,P< 0.01; male: 288 ± 23 to 317 ± 26 W,P= 0.04) and 4 mmol·L−1(female: 217 ± 13 to 227 ± 14 W,P= 0.02; male: 339 ± 43 to 364 ± 39 W,P< 0.01). No changes in Hbmass(both sexes,P= 0.8) were observed. Improvements in TT performance were not related to physiological changes (all correlationsP≥ 0.2).ConclusionsAfter 4 wk of training with BFR, the improvement in TT performance was greater than what is typical for this population. Physiological variables improved during this training block but did not explain improved TT performance.
Pothiti Hantzaroula, Child Survivors of the Holocaust in Greece: Memory, Testimony and Subjectivity
Authors: Mihăilescu Dana 
Published: April 2024

This article reviews Pothiti Hantzaroula's Child Survivors of the Holocaust in Greece: Memory, Testimony and Subjectivity (Routledge, 2020). It highlights how Hantzaroula’s book represents a needed and much welcome addition to the study of child survivors of World War II by offering students and scholars of the Holocaust a comprehensive insight into the specifics of Greece, which can serve as a basis for subsequent comparative or kindred assessments in the case of other Southeastern European countries.
Peg Abandonment and Cross-Currency Contagion
Authors: Balke Florian , Barth Andreas , Reichel Arne , Wahrenburg Mark 
Published: April 2024

Using a novel data set comprising bid–ask quotes for foreign exchange swaps from individual dealers, we examine the consequences of the Swiss National Bank’s sudden termination of the Swiss franc/euro minimum exchange rate in 2015 on other pegged currencies. Our findings indicate a spillover effect as dealer banks began to reassess the risk associated with unexpected peg terminations, subsequently leading to wider bid–ask spreads for pegged currencies. This highlights that, even in strong economies, the credibility of a currency peg is influenced not only by the actions of the respective central bank but also by the stability of other pegged currencies. This paper was accepted by Lukas Schmid, finance. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.01117 .
Simulation method for multichromatic light spots in mosaic aperture telescopes with large image planes during deployment
Authors: Tang Hongyang , Liao Zhiyuan , Jiang Jisong , Chen Mo , Xian Hao , Li Hua , Liao Sheng 
Published: April 2024

In optical systems, diffraction limits significantly impact spot simulations. This study addresses this problem by applying the Fourier transform to calculate spots in imaging systems. Typically, a 1 mm image plane suffices; however, mosaic aperture telescopes with notable wavefront discontinuities require an approximately 10 mm simulation image plane. This necessitates high sampling rates for pupils, posing challenges for conventional methods. Our model overcomes this challenge by leveraging an interpolation technique to align multiwavelength spots on a uniform image plane grid, thus effectively analyzing spot translation and spreading in imaging systems with diffraction limits.
Dual-objective two-photon microscope for volumetric imaging of dense scattering biological samples by bidirectional excitation and collection
Authors: Zhai Muyue , Yu Jing , Hu Yanhui , Yu Hang , Xie Beichen , Yu Yi , Li Dawei , Wang Aimin , Cheng Heping 
Published: April 2024

Full view observation throughout entire specimens over a prolonged period is crucial when exploring the physiological functions and system-level behaviors. Multi-photon microscopy (MPM) has been widely employed for such purposes owing to its deep penetration ability. However, the current MPM struggles with balancing the imaging depth and quality while avoiding photodamage for the exponential increasement of excitation power with the imaging depth. Here, we present a dual-objective two-photon microscope (Duo-2P), characterized by bidirectional two-photon excitation and fluorescence collection, for long-duration volumetric imaging of dense scattering samples. Duo-2P effectively doubles the imaging depth, reduces the total excitation energy by an order of magnitude for samples with a thickness five times the scattering length, and enhances the signal-to-noise ratio up to 1.4 times. Leveraging these advantages, we acquired volumetric images of a 380-μm suprachiasmatic nucleus slice for continuous 4-h recording at a rate of 1.67 s/volume, visualized the calcium activities over 4000 neurons, and uncovered their state-switching behavior. We conclude that Duo-2P provides an elegant and powerful means to overcome the fundamental depth limit while mitigating photodamages for deep tissue volumetric imaging.
Focal Distal Esophageal Dilation (Blown-Out Myotomy) After Achalasia Treatment: Prevalence and Associated Symptoms
Authors: Kuipers Thijs , Ponds Fraukje A. , Fockens Paul , Bastiaansen Barbara A.J. , Pandolfino John E. , Bredenoord Albert J. 
Published: April 2024

INTRODUCTION:
Peroral endoscopic myotomy (POEM) may result in a distended distal esophagus, referred to as a blown-out myotomy (BOM), the relevance of which is uncertain. The aim of this study was to investigate the prevalence, risk factors, and associated symptoms of BOM after achalasia treatment.

METHODS:
A data set of the locally treated patients in a randomized controlled trial comparing POEM with pneumatic dilation (PD) was analyzed. A BOM is defined as a >50% increase in esophageal diameter at its widest point in the distal esophagus between the lower esophageal sphincter and 5 cm above.

RESULTS:
Seventy-four patients were treated in our center, and 5-year follow-up data were available in 55 patients (32 patients [58%] randomized to POEM, 23 [42%] PD). In the group initially treated with POEM, the incidence of BOM increased from 11.5% (4/38) at 3 months, to 21.1% (8/38) at 1 year, 27.8% (10/36) at 2 years, and 31.3% (10/32) at 5 years. None of the patients treated with PD alone developed a BOM. Patients who developed a BOM had a higher total Eckardt score and Eckardt regurgitation component compared with patients who underwent POEM without BOM development (3 [2.75–3.25] vs 2 [1.75–3], P = 0.032, and 1 [0.75–1] vs 0 [0–1], P = 0.041). POEM patients with a BOM more often report reflux symptoms (85% [11/13] vs 46% [2/16], P = 0.023) and had a higher acid exposure time (24.5% [8–47] vs 6% [1.2–18.7], P = 0.027).

DISCUSSION:
Thirty percent of the patients treated with POEM develop a BOM, which is associated with a higher acid exposure, more reflux symptoms, and symptoms of regurgitation.
Obeticholic Acid and Insulin Sensitivity in Overweight Patients with Prediabetes
Authors: Amer H. , Nesim M. , Mansour H. , Nasr E. , Ahmed N. 
Published: April 2024

BACKGROUND. Due to its role as a risk factor for the emergence of metabolic illnesses including type 2 diabetes, cardiovascular disease, and certain cancers with pandemic evolution, obesity is a serious public health concern. Diabetes mellitus type 2 (T2DM) poses a major risk to human health. The byproducts of the breakdown of cholesterol are bile acids, which are crucial for preserving cholesterol homeostasis. Research indicates that bile acids might control insulin sensitivity, energy metabolism, and glucose tolerance. Farnesoid X receptors (FXRs) are crucial for controlling bile acid production and hepatic glucose metabolism. The ligand for FXR The semisynthetic derivative of chenodeoxycholic acid, a bile acid, is obeticholic acid (OCA). Research indicates that bile acids may be a viable therapeutic target for type 2 diabetes (T2DM) given that therapy with oleic acid (OCA) enhanced insulin sensitivity and decreased indicators of liver inflammation and fibrosis in individuals with T2DM and nonalcoholic steatohepatitis (NASH).AIM. To assess Obeticholic acid’s effectiveness in obese individuals with prediabetes.MATERIALS AND METHODS. Over the course of three months, we performed a randomized single blind placebo controlled trial on eighty-two overweight and obese patients with prediabetes in the outpatient clinic at Ain Shams University Hospital. Through block randomization, patients were split into two groups (Group A received daily oral tablets containing 5 mg of obeticholic acid, while Group B received non-sweet capsules as a placebo). Three follow-up visits were conducted to ensure adherence and monitor for any emergence of side effects.RESULTS. 82 patients of matched age and sex criteria who underwent block randomization into 2 equal groups, group (A) representing cases and group (B) the placebo controlled group, with 3 months’ regular follow up showed at end of treatment statistically significant difference in weight being lower in group (A) with p-value 0.004 with decreased parameters of glycemic profile (Fasting insulin, FPG, HOMA_IR, 2h PP, HbA1c) in group (A) with p-value <0.001 except 2hpp which p-value is 0.006. Also ALT was much decreased in group (A) with p-value <0.001. Lipid profile didn’t show significant difference between 2 groups except for TGs which deceased in follow up in group (A) with p-value <0. 001. Additionally, it should be highlighted that there was no statistically significant difference between the control group’s baseline and post-treatment data.CONCLUSION. In individuals who are overweight or obese and have insulin resistance and prediabetes, activation of FXR by OCA results in enhanced insulin sensitivity. Patients who received OCA also lost weight.