bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human induced-T-to-natural killer cells have potent anti-tumour activities
Authors: Jiang Zhiwu , Qin Le , Tang Yuou , Liao Rui , Shi Jingxuan , He Bingjia , Li Shanglin , Zheng Diwei , Cui Yuanbin , Wu Qiting , Long Youguo , Yao Yao , Wei Zhihui , Hong Qilan , Wu Yi , Mai Yuanbang , Gou Shixue , Li Xiaoping , Weinkove Robert , Norton Sam , Luo Wei , Feng Weineng , Zhou Hongsheng , Liu Qifa , Chen Jiekai , Lai Liangxue , Chen Xinwen , Pei Duanqing , Graf Thomas , Liu Xingguo , Li Yangqiu , Liu Pentao , Zhang Zhenfeng , Li Peng 
Published: March 2022

Abstract
Background
Adoptive cell therapy (ACT) is a particularly promising area of cancer immunotherapy, engineered T and NK cells that express chimeric antigen receptors (CAR) are being explored for treating hematopoietic malignancies but exhibit limited clinical benefits for solid tumour patients, successful cellular immunotherapy of solid tumors demands new strategies.

Methods
Inactivation of BCL11B were performed by CRISPR/Cas9 in human T cells. Immunophenotypic and transcriptional profiles of sgBCL11B T cells were characterized by cytometer and transcriptomics, respectively. sgBCL11B T cells are further engineered with chimeric antigen receptor. Anti-tumor activity of ITNK or CAR-ITNK cells were evaluated in preclinical and clinical studies.

Results
We report that inactivation of BCL11B in human CD8+ and CD4+ T cells induced their reprogramming into induced T-to-natural killer cells (ITNKs). ITNKs contained a diverse TCR repertoire; downregulated T cell-associated genes such as TCF7 and LEF1; and expressed high levels of NK cell lineage-associated genes. ITNKs and chimeric antigen receptor (CAR)-transduced ITNKs selectively lysed a variety of cancer cells in culture and suppressed the growth of solid tumors in xenograft models. In a preliminary clinical study, autologous administration of ITNKs in patients with advanced solid tumors was well tolerated, and tumor stabilization was seen in six out nine patients, with one partial remission.

Conclusions
The novel ITNKs thus may be a promising novel cell source for cancer immunotherapy.

Trial registration
ClinicalTrials.gov, NCT03882840. Registered 20 March 2019-Retrospectively registered.
The National Health Cluster in Yemen: assessing the coordination of health response during humanitarian crises
Authors: Al-Awlaqi Sameh , Dureab Fekri , Tambor Marzena 
Published: March 2022

AbstractYemen has been facing political, economic and social challenges since 1990. The fragility of Yemen’s situation has led to a widespread conflict in 2015, resulting in the world’s largest humanitarian crisis. Amid the humanitarian catastrophe and the collapsing health system, a platform for coordinating humanitarian health response, called the National Health Cluster, has expanded its operations across the country. The study aims to evaluate the performance of the National Health Cluster in Yemen between 2015 and 2019. A qualitative research design was employed, and ten semi-structured interviews with key Health Cluster stakeholders were conducted. The study applied the Active Learning Network for Accountability and Performance in Humanitarian Action (ALNAP) guide to evaluating humanitarian action using the Development Assistance Committee (DAC) criteria. Six evaluation criteria were selected: relevance, effectiveness, efficiency, effects, connectedness and participation. Inputs from interviews were manually transcribed and then analysed using NVivo 12 software. The study results indicate that the Health Cluster in Yemen has contributed to saving lives and strengthening the local health capacities in diseases surveillance. In addition, its positive effect was evident in improving the humanitarian health response coordination.Nevertheless, engaging health stakeholders, especially national organisations, was suboptimal. Exit strategies were lacking, while services to address mental health, non-communicable diseases, senior citizens and people with disabilities were not prioritised in the Health Cluster strategic plans and partners’ response. To ameliorate Health Cluster performance, revising its objectives and establishing a cluster-specific rapid response funding mechanism are pivotal. Furthermore, preparing the national health system for recovery and actively engaging all stakeholders in the Health Cluster’ response and strategic decisions would maximise its positive impact on Yemen’s health system and population.
The sequential mediation model of students’ willingness to continue online learning during the COVID-19 pandemic
Authors: Ngah Abdul Hafaz , Kamalrulzaman Nurul Izni , Mohamad Mohamad Firdaus Halimi , Rashid Rosyati Abdul , Harun Nor Omaima , Ariffin Nur Asma , Osman Noor Azuan Abu 
Published: March 2022

AbstractThis study explored the factors influencing students’ willingness to continue with the online learning system during the coronavirus disease 2019 (COVID-19) pandemic by adopting the stimulus–organism–response (SOR) theory. This study also incorporated e-learning readiness, performance, and satisfaction as mediators. The present study employed the purposive sampling method, whereby 2215 data of undergraduate students from a public university were gathered using an online survey and analysed using structural equation modelling (SEM) with Smart Partial Least Squares (SmartPLS). The results revealed that students’ e-learning readiness, performance, and satisfaction positively influenced their willingness to continue online learning. Besides, students’ e-learning readiness, performance, and satisfaction sequentially mediated the relationship between the online learning system quality and willingness to continue online learning. Significantly, this study provided new insights into the literature on students’ willingness to continue online learning by providing empirical evidence on the factors that support their willingness to continue online learning during the COVID-19 pandemic.
Computer vision syndrome and predictors among computer users in Ethiopia: a systematic review and meta-analysis
Authors: Adane Fentahun , Alamneh Yoseph Merkeb , Desta Melaku 
Published: March 2022

Abstract
Background
A computer is one of the most widely used office tools. The leading occupational health problem of the twenty-first century is computer vision syndrome (CVS). Research findings across Ethiopia on the magnitude and predictors of CVS among computer users are highly variable and inconsistent. Therefore, this study aimed to estimate the overall prevalence of CVS and its predictors among computer users in Ethiopia.

Methods
We searched articles in all databases and other sources. Cochrane Q test statistics and I2 tests were used. A random-effect meta-analysis model was used. In addition, the association between risk factors and CVS among computer users was examined.

Results
Eight eligible studies were included. The pooled prevalence of CVS among computer users in Ethiopia was 73.21% (95% CI 70.32–76.11). Sub-group analysis by profession has shown that the highest prevalence of CVS was observed in bank employees [73.76% (95% CI 70.40–77.13)]. The most common reported symptoms of CVS were blurred vision (34.26%; 95% CI 22.08, 46.43). The previous history of eye disease (95% CI 2.30, 5.47), inappropriate sitting position (95% CI 1.76, 3.22), the frequent use of a computer (95% CI 2.04, 3.60), and using eyeglass/spectacles (95% CI 1.10, 3.91) were significantly associated with CVS among computer users in Ethiopia.

Conclusions
According to this study, computer vision syndrome was high among computer users in Ethiopia. Computer vision syndrome (CVS) was significantly associated with a previous history of eye disease, inappropriate sitting position, frequent use of a computer, and the use of spectacles. Based on the findings, it is suggested that efforts be made to optimize computer exposure time. It is also worth noting that employees should be properly seated when using a computer. Furthermore, people with vision problems should be extra cautious when using a computer. Finally, community awareness of the safety precautions that can be taken to reduce CVS is critical.
High-speed Si-Ge avalanche photodiodes
Authors: Wang Binhao , Mu Jifang 
Published: March 2022

AbstractHigh-speed optical interconnects of data centers and high performance computers (HPC) have become the rapid development direction in the field of optical communication owing to the explosive growth of market demand. Currently, optical interconnect systems are moving towards higher capacity and integration. High-sensitivity receivers with avalanche photodiodes (APDs) are paid more attention due to the capability to enhance gain bandwidth. The impact ionization coefficient ratio is one crucial parameter for avalanche photodiode optimization, which significantly affects the excess noise and the gain bandwidth product (GBP). The development of silicon-germanium (Si-Ge) APDs are promising thanks to the low impact ionization coefficient ratio of silicon, the simple structure, and the CMOS compatible process. Separate absorption charge multiplication (SACM) structures are typically adopted in Si-Ge APDs to achieve high bandwidth and low noise. This paper reviews design and optimization in high-speed Si-Ge APDs, including advanced APD structures, APD modeling and APD receivers.
Pilot Study of a Wearable Activity Monitor During Head and Neck Radiotherapy to Predict Clinical Outcomes
Authors: Sher David J. , Radpour Sepeadeh , Shah Jennifer L. , Pham Nhat-Long , Jiang Steve , Vo Dat , Sumer Baran D. , Day Andrew T. 
Published: March 2022

PURPOSE Given the established associations between performance status and survival in a variety of cancers, there is significant interest in using a biometric wearable device (WD) to predict outcomes in the oncology population. In this pilot study, we investigated the ability of a WD to predict meaningful clinical end points in patients undergoing head and neck radiotherapy. METHODS Patients receiving head and neck definitive chemoradiotherapy or postoperative radiotherapy/chemoradiotherapy were enrolled in this pilot study, designed to show 90% compliance with using the device. Individuals were asked to wear the WD for 23 hours a day, and hospital admissions, pain medication usage, and FACT-G quality-of-life (QoL) score were prospectively recorded. RESULTS Fifty-one patients were enrolled and started using the WD, but eight patients stopped wearing it, resulting in a compliance probability of only 84%. There were 15 hospital admissions, 13 of which were planned for feeding tube placement. There was no step count threshold that predicted the need for admission or more pain medications. However, among the 25 patients with a significant reduction in FACT-G score, the average reductions in daily steps during the week and weekend before the decline were 988 ( P = .005) and 1,311 ( P = .018), respectively, and the odds of a QoL reduction were more than 4-fold higher among patients experiencing a week-to-week reduction of at least 1,000 daily steps. There was no association between heart rate and any end point. CONCLUSION Although not meeting the compliance goal, the majority of patients did use the WD. The WD signal could not identify patients requiring hospitalization or significantly more pain medication, but the finding of reduced step counts before a significant reduction in QoL is provocative.
Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study
Authors: Kowalyszyn Ruben D. , Fein Luis E. , Richardet Martin E. , Varela Mirta S. , Ortiz Eduardo , Micheri Cristian , Zarba Juan J. , Kahl Susana , Klimovsky Ezequiel , Federico Andrea A. , Cassini Jorge H. , Cortese Gustavo , Lago Nestor 
Published: March 2022

PURPOSE This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer. METHODS This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs). RESULTS A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR ( P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, –0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, –0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia. CONCLUSION Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.
Outcomes of Cervical Cancer in HIV-Positive Women Treated With Radiotherapy at a Tertiary Care Center in India
Authors: Gurram Lavanya , Mohanty Samarpita , Chopra Supriya , Grover Surbhi , Engineer Reena , Gupta Sudeep , Ghosh Jaya , Gulia Seema , Sawant Sheela , Daddi Anuprita , Deodhar Kedar , Menon Santosh , Rekhi Bharat , Shylasree T.S. , Maheshwari Amita , Mahantshetty Umesh 
Published: March 2022

PURPOSE There are limited data on management of cervical cancer in women living with HIV in the modern antiretroviral therapy era. The study aimed to evaluate outcomes and toxicities of these patients treated with radiotherapy. MATERIALS AND METHODS A retrospective analysis of HIV-positive cervical cancer patients treated with radiotherapy between 2011 and 2018 was conducted at a tertiary care center in India. RESULTS Eighty-two HIV-positive cervical cancer patients treated with radiotherapy were identified. Their median age was 45 years. Seventy-four (90%) patients received radiotherapy with curative-intent and eight patients received palliative radiotherapy. Median CD4 count at the start of treatment was 342 cells/mm3 (interquartile range: 241-531). Among patients planned for definitive radiotherapy, concurrent cisplatin was planned in 52 (70%) patients with a median of four chemotherapy cycles, and 81% (n = 60) patients received brachytherapy. Among patients who received brachytherapy, the median prescription dose was 80 Gy. Seventy-seven patients completed their prescribed treatment. At a median follow-up of 37 months, 3-year disease-free survival of patients planned with curative-intent was 54%. On multivariate analysis, treatment completion was associated with favorable disease-free survival. Grade III/IV acute gastrointestinal toxicity was seen in five (6.8%) patients, whereas 30% patients had grade III/IV acute hematologic toxicity. All these patients completed their planned radiotherapy with good supportive care. CONCLUSION Standard treatment of chemoradiation should be planned in women living with HIV with well-managed HIV presenting with locally advanced cervical cancer. Our study highlights the need for optimal management of these patients by a multidisciplinary team with intensive supportive care to ensure completion of planned treatment to achieve better outcomes.
Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma
Authors: Wang Ying , Cao Jiang , Gu Weiying , Shi Ming , Lan Jianping , Yan Zhiling , Jin Lai , Xia Jieyun , Ma Sha , Liu Yang , Li Hujun , Pan Bin , Chen Wei , Fei Xiaoming , Wang Chunling , Xie Xiaobao , Yu Liang , Wang Gang , Li Huizhong , Jing Guangjun , Cheng Hai , Zhu Feng , Sun Haiying , Sang Wei , Li Depeng , Li Zhenyu , Zheng Junnian , Xu Kailin 
Published: March 2022

PURPOSE A combination of anti–B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells induced high response rates in patients with relapsed or refractory (R/R) multiple myeloma (MM), but long-term outcomes have not been assessed yet. PATIENTS AND METHODS In this single-arm, phase II trial, patients with R/R MM received a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 106 cells/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics. RESULTS Of 69 enrolled patients, 62 received the combined infusion of anti-BCMA and anti-CD19 CAR T cells with a median follow-up of 21.3 months. The overall response rate was 92% (57/62), and complete response or better was observed in 37 patients (60%). Minimal residual disease–negativity was confirmed in 77% (43/56) of the patients with available minimal residual disease detection. The estimated median duration of response was 20.3 months (95% CI, 9.1 to 31.5). The median progression-free survival was 18.3 months (95% CI, 9.9 to 26.7), and the median overall survival was not reached. Patients with extramedullary disease had significantly inferior survival. Fifty-nine patients (95%) had cytokine release syndrome, with 10% grade 3 or higher. Neurotoxic events occurred in seven patients (11%), including 3% grade 3 or higher. Late adverse effects were rare, except for B-cell aplasia, hypogammaglobulinemia, and infections. CONCLUSION The combination of anti-BCMA and anti-CD19 CAR T cells induced durable response in patients with R/R MM, with a median progression-free survival of 18.3 months and a manageable long-term safety profile.
Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score
Authors: Burtness Barbara , Rischin Danny , Greil Richard , Soulières Denis , Tahara Makoto , de Castro Jr Gilberto , Psyrri Amanda , Brana Irene , Basté Neus , Neupane Prakash , Bratland Åse , Fuereder Thorsten , Hughes Brett G.M. , Mesia Ricard , Ngamphaiboon Nuttapong , Rordorf Tamara , Wan Ishak Wan Zamaniah , Ge Joy , Swaby Ramona F. , Gumuscu Burak , Harrington Kevin 
Published: March 2022

PURPOSE The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031 ) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS < 1 and CPS 1-19 subgroups in KEYNOTE-048. METHODS Participants with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Post hoc efficacy analyses of the PD-L1 CPS < 1 and CPS 1-19 subgroups were performed. RESULTS Of 882 participants enrolled, 128 had PD-L1 CPS < 1 and 373 had CPS 1-19. For pembrolizumab versus cetuximab-chemotherapy, the median overall survival was 7.9 versus 11.3 months in the PD-L1 CPS < 1 subgroup (hazard ratio [HR], 1.51 [95% CI, 0.96 to 2.37]) and 10.8 versus 10.1 months in the CPS 1-19 subgroup (HR, 0.86 [95% CI, 0.66 to 1.12]). For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS < 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup (HR, 0.71 [95% CI, 0.54 to 0.94]). CONCLUSION Increased efficacy of pembrolizumab or pembrolizumab-chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS < 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS ≥ 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1–expressing HNSCC.
Recalibrating Interpretations of Aldosterone Assays Across the Physiologic Range: Immunoassay and Liquid Chromatography–Tandem Mass Spectrometry Measurements Under Multiple Controlled Conditions
Authors: Brown Jenifer M , Auchus Richard J , Honzel Brooke , Luther James M , Yozamp Nicholas , Vaidya Anand 
Published: March 2022

Abstract

Context
Clinicians frequently rely on aldosterone thresholds derived from older immunoassays to diagnose primary aldosteronism. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is increasingly widespread and reported to yield lower aldosterone concentrations.

Objective
Given the health impact of incorrect interpretations of aldosterone levels, we compared measurements using LC-MS/MS and immunoassay across the full range of aldosterone physiology by evaluating distinct regulation by angiotensin II and adrenocorticotropin (ACTH).

Methods
Normotensive volunteers underwent prospective characterization of aldosterone production by immunoassay and LC-MS/MS during 4 conditions (n = 188): oral sodium suppression and restriction (to assess angiotensin II–mediated aldosterone production) and dexamethasone suppression and cosyntropin stimulation (to assess ACTH-mediated aldosterone production).

Results
Serum aldosterone concentrations by LC-MS/MS and immunoassay had a correlation of 0.69 (P &lt; .001), with good agreement (intraclass correlation 0.76; 95% CI 0.52-0.87). Aldosterone was lower by LC-MS/MS than immunoassay (median 10.5 [3.8, 21.9] vs 19.6 [9.5, 28.0] ng/dL; P &lt; .001), with an average difference of 37.2%. The most notable discrepancy was in the clinically discriminatory range &lt;20 ng/dL: 9.9 (7.1, 13.8) ng/dL using immunoassay corresponded to 5.5 (1.4, 8.9) ng/dL by LC-MS/MS (P &lt; .001). Following oral sodium suppression, the aldosterone-to-renin ratio was 4-fold higher using immunoassay (27.2 [19.7, 62.4] vs 6.4 [3.5, 19.1] ng/dL per ng/mL/hour; P &lt; .001).

Conclusion
Aldosterone measurements are substantially lower by LC-MS/MS than immunoassay across the full physiologic range, especially when aldosterone levels were less than 20 ng/dL. These findings highlight the need to recalibrate diagnostic interpretations when measuring aldosterone via LC-MS/MS and provide insights into potential biologic causes of assay differences.