bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subacute thyroiditis following recovery from COVID-19 infection: novel clinical findings from an Eastern Indian cohort
Authors: Mondal Sunetra , DasGupta Riddhi , Lodh Moushumi , Ganguly Arunangshu 
Published: April 2022

Abstract

Objective
Recent reports have suggested a link between COVID-19 infection and subacute thyroiditis (SAT). We aimed to describe variations in clinical and biochemical parameters in patients developing post-COVID SAT.

Design
Ours was a combined retrospective-prospective study on patients presenting with SAT within 3 months of recovery from COVID-19 infection, who were subsequently followed up for a further 6 months since diagnosis of SAT.

Results
Out of 670 patients with COVID-19, 11 patients presented with post-COVID-19 SAT (6.8%). Those with painless SAT (PLSAT, n = 5) presented earlier, had more severe thyrotoxic manifestations and exhibited higher C-reactive protein, interleukin 6 (IL-6), neutrophil-lymphocyte ratio and lower absolute lymphocyte count than those with painful SAT (PFSAT, n = 6). There were significant correlations of total and free T4 and total and free T3 levels with serum IL-6 levels (pall &lt;0.04). No differences were observed between patients with post-COVID SAT presenting during the first and second waves. Oral glucocorticoids were needed for symptomatic relief in 66.67% of patients with PFSAT. At 6 months of follow-up, majority (n = 9, 82%) achieved euthyroidism, while subclinical and overt hypothyroidism were found in one patient each.

Conclusions
Ours is the largest single-centre cohort of post-COVID-19 SAT reported until, demonstrating two distinct clinical presentations—without and with neck pain—depending on time elapsed since COVID-19 diagnosis. Persistent lymphopaenia during the immediate post-COVID recovery period could be a key driver of early,painless SAT. Close monitoring of thyroid functions for at least 6 months is warranted in all cases.
Phase 3, long-term, open-label extension period of safety and efficacy of belimumab in patients with systemic lupus erythematosus in China, for up to 6 years
Authors: Zhang Fengchun , Zheng Jie , Li Yang , Wang Guochun , Wang Mingjun , Su Yin , Gu Jieruo , Li Xingfu , Bass Damon , Chu Myron , Curtis Paula , DeRose Kathleen , Kurrasch Regina , Lowe Jenny , Meizlik Paige , Roth David A 
Published: April 2022

ObjectivesTo evaluate the long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in China.MethodsIn this phase 3, open-label extension period, eligible completers of study BEL113750 (NCT01345253) received intravenous belimumab 10 mg/kg monthly for ≤6 years. The primary endpoint was safety. Secondary endpoints included the SLE Responder Index (SRI)-4 response rate, severe SLE flares and changes in prednisone use. Analyses were based on observed data from the first dose of belimumab through to study end.ResultsOf the 424 patients who received belimumab, 215 (50.7%) completed the study, 208 (49.1%) withdrew and 1 patient died. Overall, 359/424 (84.7%) patients had adverse events (AEs), and 96/424 (22.6%) had serious AEs. 26/424 (6.1%) patients discontinued study treatment/withdrew from the study due to AEs. Postinfusion systemic reaction rate was 1.5 events/100 patient-years. Herpes zoster infection rate was 3.0 events/100 patient-years, of which 0.4 events/100 patient-years were serious events. One papillary thyroid cancer and one vaginal cancer were reported in year 0–1 and year 3–4, respectively. There were no completed suicides/suicide attempts and no reports of serious depression. The proportion of SRI-4 responders increased progressively (year 1, week 24: 190/346 (54.9%); year 5, week 48: 66/82 (80.5%)). Severe flares were experienced by 55/396 (13.9%) patients. For 335 patients with baseline prednisone-equivalent dose >7.5 mg/day, the number of patients with a dose reduction to ≤7.5 mg/day increased over time (year 1, week 24: 30/333 (9.0%); year 5, week 48: 36/67 (53.7%)).ConclusionsFavourable safety profile and disease control appeared to be maintained in patients with SLE in China for ≤6 years, consistent with previous belimumab studies.
Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial
Authors: Verset Gontran , Borbath Ivan , Karwal Mark , Verslype Chris , Van Vlierberghe Hans , Kardosh Adel , Zagonel Vittorina , Stal Per , Sarker Debashis , Palmer Daniel H. , Vogel Arndt , Edeline Julien , Cattan Stephane , Kudo Masatoshi , Cheng Ann-Lii , Ogasawara Sadahisa , Daniele Bruno , Chan Stephen L. , Knox Jennifer J. , Qin Shukui , Siegel Abby B. , Chisamore Michael , Hatogai Ken , Wang Anran , Finn Richard S. , Zhu Andrew X. 
Published: April 2022

Abstract

Purpose:
KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. We report results from KEYNOTE-224 (NCT02702414) cohort 2, which enrolled patients with advanced HCC and no prior systemic therapy.

Patients and Methods:
KEYNOTE-224 was an open-label, multicountry phase II trial. Eligible patients in cohort 2 had advanced HCC not amenable or refractory to locoregional therapy and not previously treated with systemic therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤2 years. Primary endpoint was objective response rate (ORR) by central imaging review per RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety/tolerability.

Results:
Between September 4, 2018, and February 20, 2019, 51 patients were allocated in cohort 2. The median time from the first dose to data cutoff (January 19, 2021) was 27 months (range, 23–29). ORR was 16% [95% confidence interval (CI), 7–29] and was similar across key subgroups. Median DOR was 16 months (range, 3–24+), and DCR was 57%. The median PFS was 4 months (95% CI, 2–8), and median TTP was 4 months (95% CI, 3–9). Median OS was 17 months (95% CI, 8–23). Grade ≥3 treatment-related adverse events occurred in 16% of patients.

Conclusions:
In patients with advanced HCC with no prior systemic therapy, pembrolizumab provided durable antitumor activity, promising OS, and had a safety profile consistent with previous observations. These findings support further evaluation of pembrolizumab-based regimens for HCC.
Single-Cell RNA Sequencing Unveils the Clonal and Transcriptional Landscape of Cutaneous T-Cell Lymphomas
Authors: Gaydosik Alyxzandria M. , Stonesifer Connor J. , Khaleel Alexandra E. , Geskin Larisa J. , Fuschiotti Patrizia 
Published: April 2022

Abstract

Purpose:
Clonal malignant T lymphocytes constitute only a fraction of T cells in mycosis fungoides skin tumors and in the leukemic blood of Sézary syndrome, the classic types of cutaneous T-cell lymphomas. However, lack of markers specific for malignant lymphocytes prevents distinguishing them from benign T cells, thus delaying diagnosis and the development of targeted treatments. Here we applied single-cell methods to assess the transcriptional profiles of both malignant T-cell clones and reactive T lymphocytes directly in mycosis fungoides/Sézary syndrome patient samples.

Experimental Design:
Single-cell RNA sequencing was used to profile the T-cell immune repertoire simultaneously with gene expression in CD3+ lymphocytes from mycosis fungoides and healthy skin biopsies as well as from Sézary syndrome and control blood samples. Transcriptional data were validated in additional advanced-stage mycosis fungoides/Sézary syndrome skin and blood samples by immunofluorescence microscopy.

Results:
Several nonoverlapping clonotypes are expanded in the skin and blood of individual advanced-stage mycosis fungoides/Sézary syndrome patient samples, including a dominant malignant clone as well as additional minor malignant and reactive clones. While we detected upregulation of patient-specific as well as mycosis fungoides– and Sézary syndrome–specific oncogenic pathways within individual malignant clones, we also detected upregulation of several common pathways that included genes associated with cancer cell metabolism, cell-cycle regulation, de novo nucleotide biosynthesis, and invasion.

Conclusions:
Our analysis unveils new insights into mycosis fungoides/Sézary syndrome pathogenesis by providing an unprecedented report of the transcriptional profile of malignant T-cell clones in the skin and blood of individual patients and offers novel prospective targets for personalized therapy.
Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs
Authors: Rohrer Bley Carla , Wolf Friederike , Gonçalves Jorge Patrik , Grilj Veljko , Petridis Ioannis , Petit Benoit , Böhlen Till T. , Moeckli Raphael , Limoli Charles , Bourhis Jean , Meier Valeria , Vozenin Marie-Catherine 
Published: April 2022

Abstract

Purpose:
The FLASH effect is characterized by normal tissue sparing without compromising tumor control. Although demonstrated in various preclinical models, safe translation of FLASH-radiotherapy stands to benefit from larger vertebrate animal models. Based on prior results, we designed a randomized phase III trial to investigate the FLASH effect in cat patients with spontaneous tumors. In parallel, the sparing capacity of FLASH-radiotherapy was studied on mini pigs by using large field irradiation.

Experimental Design:
Cats with T1-T2, N0 carcinomas of the nasal planum were randomly assigned to two arms of electron irradiation: arm 1 was the standard of care (SoC) and used 10 × 4.8 Gy (90% isodose); arm 2 used 1 × 30 Gy (90% isodose) FLASH. Mini pigs were irradiated using applicators of increasing size and a single surface dose of 31 Gy FLASH.

Results:
In cats, acute side effects were mild and similar in both arms. The trial was prematurely interrupted due to maxillary bone necrosis, which occurred 9 to 15 months after radiotherapy in 3 of 7 cats treated with FLASH-radiotherapy (43%), as compared with 0 of 9 cats treated with SoC. All cats were tumor-free at 1 year in both arms, with one cat progressing later in each arm. In pigs, no acute toxicity was recorded, but severe late skin necrosis occurred in a volume-dependent manner (7–9 months), which later resolved.

Conclusions:
The reported outcomes point to the caveats of translating single-high-dose FLASH-radiotherapy and emphasizes the need for caution and further investigations.
See related commentary by Maity and Koumenis, p. 3636
Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102
Authors: Brashears Caitlyn B. , Prudner Bethany C. , Rathore Richa , Caldwell Katharine E. , Dehner Carina A. , Buchanan Jane L. , Lange Sara E.S. , Poulin Neal , Sehn Jennifer K. , Roszik Jason , Spitzer Dirk , Jones Kevin B. , O'Keefe Regis , Nielsen Torsten O. , Taylor Eric B. , Held Jason M. , Hawkins William , Van Tine Brian A. 
Published: April 2022

Abstract

Purpose:
To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.

Experimental Design:
ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro and in vivo.

Results:
ME1 absence in SS was confirmed in clinical samples, SS cell lines, and an SS tumor model. Investigation of SS glucose metabolism revealed that ME1-null cells exhibit higher rates of glycolysis and higher flux of glucose into the pentose phosphate pathway (PPP), which is necessary to produce NADPH. Evaluation of cellular redox homeostasis demonstrated that ME1 absence shifts dependence from the glutathione system to the thioredoxin system. Concomitantly, ME1 absence drives the accumulation of ROS and labile iron. ROS and iron accumulation enhances the susceptibility of ME1-null cells to ferroptosis induction with inhibitors of xCT (erastin and ACXT-3102). In vivo xenograft models of ME1-null SS demonstrate significantly increased tumor response to ACXT-3102 compared with ME1-expressing controls.

Conclusions:
These findings demonstrate the translational potential of targeting redox homeostasis in ME1-null cancers and establish the preclinical rationale for a phase I trial of ACXT-3102 in SS patients.
See related commentary by Subbiah and Gan, p. 3408
Policy paradoxes and the Vulnerable Persons Resettlement Scheme: How welfare policies impact resettlement support
Authors: Haycox Hannah 
Published: April 2022

The Vulnerable Persons Resettlement Scheme (VPRS) comprised the UK government's primary response to persons forcibly displaced by the Syrian civil war. Recipients were granted immediate recourse to public funds and a locally-based 12-month integration support plan, designed at the discretion of practitioners. Drawing on forty in-depth interviews with refugees and practitioners in two areas with contrasting local approaches, this article explores the tensions that emerged when broader central government policies (distinct from the VPRS), intersected with resettlement support in recipients’ lives. Two current welfare reforms are identified and evaluated as having impacted resettled families’ housing experiences: firstly; the Two-Child Limit and secondly; the Benefit Cap. The article demonstrates how the financial precarity produced by both policies undermined local practitioners’ resettlement support. In doing so, the article challenges dominant policy narratives of exceptionality, locating those resettled within the routinised systems of precarity and conditionality embedded in the welfare system.
Efficacy of supine trans-abdominal pronated shock head ESWL for treatment of distal ureteric stones: A pilot study
Authors: Sarkar Debansu , Wakle Dhansagar U , Pal Dilip Kumar 
Published: April 2022

Objective: To evaluate the efficacy of extracorporeal shockwave lithotripsy (ESWL) in supine trans-abdominal approach for distal ureteric calculi and to determine the variables that could affect the outcome results. Materials and methods: Between November 2019 and January 2021, 172 patients with a solitary distal ureteric calculus were treated with ESWL in supine position with a pronated shock wave head against the anterior abdominal wall. The outcome of treatment evaluated and the clinical and radiological findings, as well as stone characteristics, were reviewed and correlated with the stone-free rate (SFR). Results: Overall SFR was 84.84% (140/165). Those with stone clearance, 83.57% (117/140) cleared after one session and 16.42% (23/140) needed more than one session. Only three factors had a significant impact on SFR, that is stone length, stone width, stone attenuation. For stone length ⩽ 9 mm SFR was 93.44% (114/122) compared to 60.46% (26/43) for stone length of 10–12 mm ( p < 0.00001). There were statistically significant increased SFR for stones with attenuation of <0.0001 and for the mean stone width of 8.02 mm ( p < 0.00001). Stone localisation was easy with good patient comfort. Conclusion: Supine trans-abdominal ESWL is a new, effective and safe form of treatment for distal ureteric calculi. The stone length, stone width along with stone attenuation were the only significant predictors of stone free status in supine position.
Recycled thermoplastic polyurethane as a coupling agent in automotive polypropylene compounds with coconut fibers
Authors: Guillén-Mallette Javier , Valadez-González Alex , Rosado-Sánchez Silvia Isabel 
Published: April 2022

This study evaluates the effect of recycled thermoplastic polyurethane (RTPU) on the Izod impact resistance of polypropylene (PP) compounds with 50% coconut fibers arranged randomly. The Izod impact resistance was compared to the performance of a commercial coupling agent (CCA) of maleic anhydride grafted PP copolymer (MAPP). The PP compounds were made with 0, 2.5, and 5% by weight of RTPU or CCA, and with 50% of short or long coconut fibers, in the form of plates molded by thermo-compression, where the plastic components were previously extruded in the form of filaments. The morphology of the resulting materials was studied by scanning electron microscopy (SEM). The functional groups and their possible interactions present were determined by Fourier transform infrared spectroscopy (FTIR). Furthermore, the interfacial shear strength between the polymeric matrix and the coconut fiber was determined. The results showed a higher Izod impact resistance and a higher adhesion between long coconut fiber and PP when they contain 5% RTPU. This is explained by the higher interfacial shear strength between them given by the chemical and/or physical interaction between functional groups such as the lignin of coconut fibers and the isocyanate groups of RTPU, which in turn determined the shortest critical length of coconut fiber. The impact resistance values ranged from 19.8 to 24.4 J/m for mixtures of PP with short coconut fibers and 39.9–71.7 J/m for PP with long coconut fibers.
Factors contributing to neck pain in patients with degenerative cervical myelopathy: A prospective multicenter study
Authors: Inose Hiroyuki , Hirai Takashi , Yoshii Toshitaka , Kimura Atsushi , Takeshita Katsushi , Inoue Hirokazu , Maekawa Asato , Endo Kenji , Miyamoto Takuya , Furuya Takeo , Nakamura Akira , Mori Kanji , Kanbara Shunsuke , Imagama Shiro , Seki Shoji , Matsunaga Shunji , Takahashi Kunihiko , Okawa Atsushi 
Published: April 2022

Purpose Although the understanding of the mechanisms of low back pain due to spinopelvic sagittal imbalance has strengthened, the understanding of the mechanisms of neck pain remains insufficient. Thus, this study aimed to identify the factors associated with preoperative and postoperative neck pain in patients with degenerative cervical myelopathy who underwent laminoplasty. Methods In this prospective multicenter study, we prospectively enrolled patients who were scheduled for laminoplasty for degenerative cervical myelopathy. The associations between different variables and the Numerical Pain Rating Scale (NRS) scores for neck pain were investigated using univariate and multiple linear regression models. Results In total, 92 patients were included in the current study. The univariate analysis showed that age, sex, cervical lordosis in neutral and extension, and thoracic kyphosis were significantly associated with the preoperative NRS score for neck pain; moreover, preoperative cervical lordosis in extension and range of motion and postoperative cervical lordosis in neutral, flexion, and extension were significantly associated with the postoperative NRS Scale score for neck pain. Stepwise multiple regression analysis showed that the independent factors contributing to preoperative neck pain were preoperative cervical lordosis in extension, sex, and age. The independent preoperative predictor and contributor to postoperative neck pain were preoperative cervical lordosis in extension and postoperative cervical lordosis in extension, respectively. Conclusions Cervical lordosis in extension showed significant association with neck pain in patients with degenerative cervical myelopathy. Therefore, when performing laminoplasty for patients with a low cervical lordosis in extension, attention should be paid to residual postoperative neck pain.
Increased signal intensity, not volume variation of infrapatellar fat pad in knee osteoarthritis: A cross-sectional study based on high-resolution magnetic resonance imaging
Authors: He Jinshen , Ba Hongliang , Feng Jing , Peng Cheng , Liao Yunjie , Li Lifeng , Cao Xu , Wang Zili , Shen Minren , Wu Song 
Published: April 2022

Background Infrapatellar fat pad (IPFP) is regarded as an essential knee tissue involved in osteoarthritis (OA) for its potential structural-related or metabolism-related function. This cross-sectional study aims to identify which part is more related to OA. Methods Patients with knee OA ( n = 53) and healthy controls ( n = 54) were prospectively recruited. Based on high-resolution magnetic resonance imaging with a slice thickness of only 0.35 mm, IPFP structural-related parameters (volume and maximal area), metabolism-related parameter (signal), degeneration indicators, and patellar maltracking indicators (patellar translation, patellofemoral angle, and Insall-Salvati ratio) were measured. IPFP volume (maximal area, and signal) was compared between healthy controls and OA patients. The level of significance for all comparisons was set as .05. Results OA patients had higher IPFP signal (672.9 ± 136.9 vs 567.3 ± 63.6, p = .009), but no significant difference in IPFP volume or maximal area compared with healthy controls. In healthy controls, IPFP signal was positively associated with age ( β = 1.481; 95% CI: 0.286–2.676; p = .018); IPFP maximal area was positively related to Insall-Salvati ratio ( β = 0.001; 95% CI: 0.0003–0.0017; p = .039), but not associated with patellar translation and patellofemoral angle. In OA patients, IPFP signal was positively associated with cartilage loss ( β = 0.005; 95% CI: 0.003–0.007; p = .013); no correlation between knee pain and IPFP volume or maximal area was observed. Conclusions The metabolism-related function of IPFP, which can be reflected by the IPFP signal, might play a more critical role in OA progression than its structural function.
Comparison of Icare HOME and non-contact tonometer in intraocular pressure measurement in the early stage after ICL V4c implantation
Authors: Ye Yuhao , Yang Fangwen , Ding Lan , Xia Fei , Niu Lingling , Wang Xiaoying , Zhao Jing , Zhou Xingtao 
Published: April 2022

Purpose To investigate the characteristics of intraocular pressure (IOP) measurements using the Icare HOME rebound tonometer (RBT) and non-contact tonometer (NCT) during the early stage after implantable collamer lens (ICL) V4c implantation, and to assess the agreement between the two methods. Methods This prospective case series study included 104 eyes of 53 patients (mean age 28.77  ±  5.34 years), who underwent ICL V4c implantation. IOP was measured preoperatively, and at 0.5, 1, 2, 4, and 24 h postoperatively by Icare HOME and NCT, respectively. Results All surgeries were uneventful. IOP measurements by Icare and NCT preoperatively were 14.03  ±  2.90 mmHg and 14.09  ±  2.87 mmHg, respectively.The corresponding values were 12.56  ±  8.09 mmHg and 14.12  ±  6.52 mmHg (P > 0.05) at postoperative 0.5 h, 19.21  ±  8.74 mmHg and 19.60  ±  7.66 mmHg at postoperative 1 h (P > 0.05), 21.21  ±  8.10 mmHg and 20.31  ±  6.93 mmHg at postoperative 2 h (P > 0.05), 16.11  ±  5.89 mmHg and 17.04  ±  4.84 mmHg at postoperative 4 h (P > 0.05), and 14.04  ±  3.88 mmHg and 14.78  ±  2.80 mmHg at postoperative 24 h, respectively (P > 0.05). There was good agreement based on intraclass correlation coefficients (ICCs) between NCT and Icare HOME (all ICCs > 0.6 at different time points [range, 0.6986–0.956]). The Bland-Altman plot showed a mean percentage of over 95.81% of the points falling within the limits of agreement. There was a significant difference in the low IOP measurements (<10 mmHg) between Icare HOME and NCT (7.28  ±  2.55 vs. 10.65  ±  2.48, P < 0.001). Conclusion Icare HOME can be used for IOP measurement after ICL V4c implantation and demonstrated good agreement with NCT, except in cases with low intraocular pressure (<10 mmHg).