bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program
Authors: Illini Oliver , Hochmair Maximilian Johannes , Fabikan Hannah , Weinlinger Christoph , Tufman Amanda , Swalduz Aurélie , Lamberg Kristina , Hashemi Sayed M. S. , Huemer Florian , Vikström Anders , Wermke Martin , Absenger Gudrun , Addeo Alfredo , Banerji Shantanu , Calles Antonio , Clarke Stephen , Di Maio Massimo , Durand Alice , Duruisseaux Michaël , Itchins Malinda , Kääränien Okko-Sakari , Krenn Florian , Laack Eckart , de Langen Adrianus Johannes , Mohorcic Katja , Pall Georg , Passaro Antonio , Prager Gerald , Rittmeyer Achim , Rothenstein Jeffrey , Schumacher Michael , Wöll Ewald , Valipour Arschang 
Published: June 2021

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.
Individual, socio-cultural, and health facility factors affecting men’s involvement in facility-based childbirth in Southwest, Ethiopia: A mixed method study
Authors: Hailemariam Shewangizaw , Abayneh Mengistu , Genetu Amare 
Published: June 2021

Introduction: Traditionally, men are not supposed to take part in maternal health issues in many cultures. Nevertheless, pregnancy care and childbirth are the most crucial matters of reproductive health influenced by men. Hence, the aim of this study was to identify individual, sociocultural, and health facility factors affecting men’s involvement in facility-based childbirth in Southwest, Ethiopia. Objectives: The aim of this study was to identify individual, sociocultural, and health facility factors affecting men’s involvement in facility-based childbirth in Southwest, Ethiopia. Methods: A community-based cross-sectional study accompanied with a qualitative method was carried out from 1 July to 30 August 2019. A multistage cluster sampling technique was employed to recruit study participants. Descriptive statistics, frequencies, proportions, and mean were calculated, and the results of the analysis were presented in text, tables, and graphs. A multivariate logistic regression model was fitted to investigate the independent effect of each explanatory variable on the likelihood of men’s involvement in facility-based childbirth. Qualitative data were analyzed thematically using OpenCode 4.0 software. Results: Out of 800 men, only 36.5% (95% confidence interval: 33.3%–39.6%) were found to have involved in facility-based childbirth. Several factors were associated with men’s involvement in facility-based childbirth of this, being in the age group of 40–49 (adjusted odds ratio 5.04, 95% confidence interval: 2.49–10.20), attaining secondary education and above (adjusted odds ratio 2.14, 95% confidence interval: 1.53–5.60), and having sufficient knowledge of danger signs during pregnancy (adjusted odds ratio 5.65, 95% confidence interval: 3.25–7.46) associated with men’s involvement in facility-based childbirth. Conclusion: Relevant entities had better design-specific educational programs targeting younger age groups, those with lower schooling, and had previous bad obstetrics outcomes. Involving elders and religious leaders in the reproductive health program could also help in overcoming the existing cultural barriers. Moreover, creating a men-friendly facility environment and extensively engaging medias are suggested to improve men’s involvement in the study area.
A cohort analysis of patients receiving neoadjuvant androgen deprivation therapy prior to robot-assisted laparoscopic prostatectomy during the Covid-19 pandemic
Authors: Bennett Sahan S , Leung Hing Y , Ahmad Imran 
Published: June 2021

Objectives: The purpose of this study was to investigate localised prostate cancer treated with or without neoadjuvant androgen deprivation therapy prior to robot-assisted laparoscopic prostatectomy, and the impact of Covid-19 treatment disruption, on clinico-pathologic outcomes. Patients and methods: Data was retrospectively collected from 124 consecutive patients treated with robot-assisted laparoscopic prostatectomy between November 2019–September 2020. Sixty-two patients were treated before 13 March 2020 (historic cohort) and 62 afterwards (covid cohort). Thirty-seven patients in the covid cohort additionally received neoadjuvant androgen deprivation therapy (mean duration of 3 months) consisting of bicalutamide 150 mg once a day for 4 weeks, with leuprolide 3.75 mg monthly injections commencing after week 1, up until the date of surgery. Results: Statistical analysis found no difference in peri-operative measures and length of stay for patients treated with or without neoadjuvant androgen deprivation therapy. Patients with delayed surgical treatment offered neoadjuvant androgen deprivation therapy showed a trend towards a reduction in positive surgical margins ( p=0.134), N1 disease ( p=0.424) and pathological down-staging (50% patients with pT2 disease). Patients within the covid cohort experienced significantly increased detectable prostate-specific antigen levels ( p<0.007). Conclusion: Our study demonstrated that a three-month duration of neoadjuvant androgen deprivation therapy prior to robot-assisted laparoscopic prostatectomy may improve pathological outcomes but this time-frame is inadequate to influence detectable prostate-specific antigen levels. Covid-19-related treatment delays led to significantly increased detectable prostate-specific antigen levels. Level of evidence: 2b
A Novel Surgical Method for Treating Symptomatic Incomplete Atypical Femoral Fracture using Percutaneous Elastic Intramedullary Nailing
Authors: Park Joon Hong , Cho Yoon Je , Chun Young-Soo , Rhyu Kee Hyung 
Published: June 2021

Purpose: To introduce the principles and procedure of percutaneous elastic intramedullary nailing (PEIN) as a treatment for symptomatic incomplete atypical femoral fracture (SIAFF). Methods: From October 2014 to April 2019, 6 cases of SIAFF were treated with PEIN. Two pre-bent 4-mm stainless-steel nails were used to apply compressive force to the fracture site. The antegrade method was used for proximal fractures and the retrograde method for middle and distal femoral fractures. The femoral bowing angle in the coronal and sagittal planes, and the time required for callus formation and union, were evaluated on plain radiographs in both planes. Thigh pain, tenderness, and complications were also assessed. Results: The mean operating time was 65.00 ± 22.64 min. No case progressed to complete atypical fracture. In one case, fracture occurred around the point of nail entry after the patient fell from a chair on postoperative day 7. The incomplete fracture lines were united in 5 cases, after excluding one case with a complication. The time taken to confirm endocortical callus formation, fracture line disappearance, and clinical union was 2.11 ± 0.53, 6.45 ± 4.10, and 6.45 ± 3.65 months, respectively. Conclusions: PEIN is a quick, simple but effective treatment for SIAFF that considers the fracture mechanism and is applicable to cases with severe femoral bowing. Level of evidence: Level IV, case series.
Correlation of medial longitudinal arch morphology with body characteristics and locomotive function in community-dwelling older women: A cross-sectional study
Authors: Nakao Hidetoshi , Imaoka Masakazu , Hida Mitsumasa , Imai Ryota , Tazaki Fumie , Morifuji Takeshi , Hashimoto Masashi , Nakamura Misa 
Published: June 2021

Purpose: This cross-sectional study aimed to investigate the effects of foot arch deformities on physical characteristics, muscular strength, and motor function in older women depending on the presence or absence of pain. Methods: Overall, 145 community-dwelling women aged 65 to 90 years were included in this study. We measured the foot arch height ratio (AHR, dorsal height/truncated foot length) and classified participants with AHR values above, below, or within 1.5 standard deviations into the high-arched group (HAG), Low-Arched Group (LAG), or normal-arched group (NAG), respectively. We also compared body characteristics (age, height, weight, body mass index (BMI), and skeletal mass index), muscle strength (handgrip strength and intrinsic foot strength (IFS)), and locomotive function (two-step value and gait speed) among the three groups. Results: Locomotive examination and muscle strength showed significant differences among the three groups only in the presence of pain; in the two-step test, HAG, NAG, and LAG values were 0.98 cm/cm, 1.19 cm/cm, and 1.18 cm/cm, respectively. The IFS measured 19.2 N, 24.2 N, 31.0 N, respectively, in the HAG, NAG, and LAG. Conclusion: This study suggests that decreased IFS affects the mobility function of high-arched feet in older women. Although there was no significant difference in the evaluation of pain, HAG showed the highest average value, which is considered to contribute to the decreased two-step value. It has been suggested that a high-arched foot in the presence of pain is associated with IFS weakness and may affect the decline of mobility function in older women.
Outcomes After Deepening Trochleoplasty and Concomitant Realignment in Patients With Severe Trochlear Dysplasia With Chronic Patellofemoral Pain: Results at 2-Year Follow-up
Authors: Zimmermann Felix , Milinkovic Danko Dan , Balcarek Peter 
Published: June 2021

Background: Abnormal patellofemoral joint stress appears to have major relevance in a subgroup of patients with patellofemoral pain (PFP). Purpose: To evaluate whether patients with chronic PFP and trochlear dysplasia–induced patellofemoral joint malalignment benefit from a deepening trochleoplasty procedure with the aim of improving patellotrochlear congruence. Study Design: Case series; Level of evidence, 4. Methods: Included were 15 patients (male/female, 1/14; mean age, 30.3 years [range, 19-51 years]) with 8.8 years (range, 1-20 years) of chronic PFP and severe trochlear dysplasia. All patients underwent correction of patellotrochlear malalignment with deepening trochleoplasty and concomitant realignment procedures. The Kujala score and a numerical analog scale (0-10) for intensity of pain were used to assess symptoms preoperatively and at 12 and 24 months postoperatively. Pre- and postoperative magnetic resonance imaging (MRI) scans from the patients were compared with the MRI scans of age- and sex-matched controls regarding the patellotrochlear contact area and contact ratio, patellar tilt, patellotrochlear index, and lateral trochlear inclination (LTI) angle. Results: The Kujala score increased from a mean of 55 (range, 15-81) preoperatively to 82.5 (range, 53-98) after 12 months (95% CI, –42.56 to –12.37; P < .001) and to 84.2 (range, 59-99) after 24 months (95% CI, –44.29 to –14.11; P < .001). The intensity of PFP decreased from 5.7 (range, 3-10) preoperatively to 1.4 (range, 0-4) after 12 months (95% CI, 2.57 to 5.96; P < .001) and had a mean of 1.6 (range, 0-6) after 24 months (95% CI, 2.44 to 5.75; P < .001). Preoperatively, parameters in the study group indicated significant patellotrochlear malalignment, which improved and normalized (except for the LTI angle) postoperatively compared with the values of the control group ( P > .05). Conclusion: In a subgroup of patients with chronic PFP due to severe trochlear dysplasia, deepening trochleoplasty and concomitant realignment procedures significantly reduced pain and improved knee joint function while normalizing patellotrochlear congruence.
Reviving a Heritage in Peril: India’s Endangered Traditions of Cotton and Wool
Authors: Iyengar Sushma 
Published: June 2021

This article traces the journey of two indigenous textile fibres—Kala cotton and Desi Oon—and the efforts of farmers, pastoralists, craft artisans and Khamir, to conserve, sustain and promote the natural and cultural heritage that have nourished these fibres. It recreates the revival of these fibres in Kutch, a semi-arid region of India, and unfolds the technical, cultural and creative challenges that have accompanied this process—from land to the loom. Large-scale shifts in Indian agriculture have marked a significant breakdown of the value loops and deep interdependent economies between farmers, spinners, weavers, dyers and tailors. First, in the nineteenth century, when the cultivation of short staple indigenous varieties of cotton shifted to long staple cotton, which could feed the mills of Britain; and then in the late twentieth century when a global push towards hybrid, genetically modified varieties of cotton strode over the farming of more resilient local cotton varieties. Similarly, across India, vast genetic resource of sheep, yak and camels, in particular, have, for centuries, been conserved and bred by the nomadic pastoral communities of these regions. Even two and a half decade ago, the animal’s fibre was used extensively by the pastoralists themselves and fetched them a market price for the wool that was almost equal to that of meat. However, with India becoming a major sheep meat producing country, accompanied by the relaxation of tariffs on wool imports in the early nineties, the Indian wool market has moved completely to softer, longer staple wool from New Zealand, Australia and the Middle East. Today, this is the only natural fibre in which India is deficient despite having the third largest number of sheep in the world! The process of conserving indigenous cotton seeds, sheep breeds, their fibres and a range of associated textile crafts, challenge all the essential premises on which the political economy of contemporary textiles rest. However hope comes in many forms—the intense climatic variabilities and growing vulnerabilities to climate change, is compelling farmers and pastoralists to revisit the choices they have been compelled to adopt by a globalized market economy. Their growing understanding and need to revive their local cotton seeds and animal breeds, which are more adaptable and resilient to climatic variabilities, hold out a tremendous opportunity to transform the landscape of indigenous textile fibres. Through her experiences, the author stitches together a story of localization wherein Khamir attempts to restore a lost heritage and the bonds between farmers, pastoralists, spinners, weavers and dyers.
Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity
Authors: Park Joonhee , Daniels Jay , Wartewig Tim , Ringbloom Kimberly G. , Martinez-Escala Maria Estela , Choi Sara , Thomas Jane J. , Doukas Peter G. , Yang Jingyi , Snowden Caroline , Law Calvin , Lee Yujin , Lee Katie , Zhang Yancong , Conran Carly , Tegtmeyer Kyle , Mo Samuel H. , Pease David R. , Jothishankar Balaji , Kwok Pui-Yan , Abdulla Farah R. , Pro Barbara , Louissaint Abner , Boggon Titus J. , Sosman Jeffrey , Guitart Joan , Rao Deepak , Ruland Jürgen , Choi Jaehyuk 
Published: June 2021

Abstract
Cutaneous T-cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled representative samples of CTCLs from patients with diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. Two mutations have never been described in any cancer. Functionally, multiple mutations augment T-cell receptor–dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T-cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways that drive diverse disease phenotypes.
Cereblon enhancer methylation and IMiD resistance in multiple myeloma
Authors: Haertle Larissa , Barrio Santiago , Munawar Umair , Han Seungbin , Zhou Xiang , Vogt Cornelia , Fernández Rafael Alonso , Bittrich Max , Ruiz-Heredia Yanira , Da Viá Matteo , Zovko Josip , Garitano-Trojaola Andoni , Bolli Niccolò , Ruckdeschel Anna , Stühmer Thorsten , Chatterjee Manik , Kull Miriam , Krönke Jan , Agirre Xabier , Martin-Subero Jose I. , Raab Peter , Einsele Hermann , Rasche Leo , Martinez-Lopez Joaquin , Haaf Thomas , Kortüm K. Martin 
Published: June 2021

Abstract
Cereblon is the direct binding target of the immunomodulatory drugs (IMiDs) that are commonly used to treat multiple myeloma (MM), the second most frequent hematologic malignancy. Patients respond well to initial treatment with IMiDs, but virtually all patients develop drug resistance over time, and the underlying mechanisms are poorly understood. We identified an as yet undescribed DNA hypermethylation in an active intronic CRBN enhancer. Differential hypermethylation in this region was found to be increased in healthy plasma cells, but was more pronounced in IMiD-refractory MM. Methylation significantly correlated with decreased CRBN expression levels. DNA methyltransferase inhibitor (DNTMi) in vitro experiments induced CRBN enhancer demethylation, and sensitizing effects on lenalidomide treatment were observed in 2 MM cell lines. Thus, we provide first evidence that aberrant CRBN DNA methylation is a novel mechanism of IMiD resistance in MM and may predict IMiD response prior to treatment.
Infrared thermography for assessment of thoracic paravertebral block: a prospective observational study
Authors: Zhang Shuang , Liu Yong , Liu Xiaohu , Liu Tianzhu , Li Pengcheng , Mei Wei 
Published: June 2021

Abstract
Background
There was no “gold standard” to assess the success or failure of thoracic paravertebral block (TPVB). Measurement of skin temperature with infrared thermography (IT) would be a reliable method to evaluate the effectiveness of regional blocks. This study aimed to explore the feasibility of using skin temperature difference (Td) determined by IT between the blocked and unblocked side to predict the spread of TPVB.

Methods
Sixty-one patients undergoing elective unilateral breast or thoracoscopic surgery were enrolled in this prospective observational study. TPVB was performed at T4 and T5 under real-time ultrasound guidance with 10 mL of 0.4% ropivacaine for each patient, respectively. Td between the blocked and unblocked side were measured with IT from T2 to T10 at the anterior chest wall before TPVB and 5 min, 10 min, 15 min and 20 min after TPVB. Pinprick test was performed at 20 min after TPVB. Successful TPVB was defined as no sensation to pinprick in 3 or more adjacent dermatomes corresponding to the site of injection at 20 min after TPVB. Td was compared to pinprick test for evaluating its effectiveness in predicting the success of TPVB. The sensitivity, specificity, and cut-off value of Td for predicting successful TPVB were determined by receiver operator characteristic (ROC) curve analysis.

Results
Compared with the baseline value before block, Td from T2 to T10 were significantly increased at each time point in successful blocks. In failed blocks, Td was not increased in any dermatome. The increase of Td at T4-T7 was more than 1 °C 20 min after successful TPVB. Fifteen minutes after block, Td increase at T4 had the greatest potential to predict block success. The area under the ROC curve was 0.960 at a cut-off value of 0.63 °C with a sensitivity of 83.3% and a specificity of 100.0%.

Conclusions
This study suggested that the increase of Td at T4 dermatome determined by IT between the blocked and unblocked side is an early, quantitative, and reliable predictor of successful TPVB.

Trial registration
Clinical trial registration: NCT04078347.