bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL
Authors: Siddiqi Tanya , Soumerai Jacob D. , Dorritie Kathleen A. , Stephens Deborah M. , Riedell Peter A. , Arnason Jon , Kipps Thomas J. , Gillenwater Heidi H. , Gong Lucy , Yang Lin , Ogasawara Ken , Thorpe Jerill , Wierda William G. 
Published: October 2021

AbstractBruton tyrosine kinase inhibitors (BTKi) and venetoclax are currently used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually develop resistance to these therapies, underscoring the need for effective new therapies. We report results of the phase 1 dose-escalation portion of the multicenter, open-label, phase 1/2 TRANSCEND CLL 004 (NCT03331198) study of lisocabtagene maraleucel (liso-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory CLL/SLL. Patients with standard- or high-risk features treated with ≥3 or ≥2 prior therapies, respectively, including a BTKi, received liso-cel at 1 of 2 dose levels (50 × 106 or 100 × 106 CAR+ T cells). Primary objectives included safety and determining recommended dose; antitumor activity by 2018 International Workshop on CLL guidelines was exploratory. Minimal residual disease (MRD) was assessed in blood and marrow. Twenty-three of 25 enrolled patients received liso-cel and were evaluable for safety. Patients had a median of 4 (range, 2-11) prior therapies (100% had ibrutinib; 65% had venetoclax) and 83% had high-risk features including mutated TP53 and del(17p). Seventy-four percent of patients had cytokine release syndrome (9% grade 3) and 39% had neurological events (22% grade 3/4). Of 22 efficacy-evaluable patients, 82% and 45% achieved overall and complete responses, respectively. Of 20 MRD-evaluable patients, 75% and 65% achieved undetectable MRD in blood and marrow, respectively. Safety and efficacy were similar between dose levels. The phase 2 portion of the study is ongoing at 100 × 106 CAR+ T cells. This trial was registered at clinicaltrials.gov as NCT03331198.
Perturbed NK-cell homeostasis associated with disease severity in chronic neutropenia
Authors: Sohlberg Ebba , Pfefferle Aline , Heggernes Ask Eivind , Tschan-Plessl Astrid , Jacobs Benedikt , Netskar Herman , Lorenz Susanne , Kanaya Minoru , Kosugi-Kanaya Mizuha , Meinke Stephan , Mörtberg Anette , Höglund Petter , Sundin Mikael , Carlsson Göran , Palmblad Jan , Malmberg Karl-Johan 
Published: October 2021

Abstract
Neutrophils have been thought to play a critical role in terminal differentiation of NK cells. Whether this effect is direct or a consequence of global immune changes with effects on NK-cell homeostasis remains unknown. In this study, we used high-resolution flow and mass cytometry to examine NK-cell repertoires in 64 patients with neutropenia and 27 healthy age- and sex-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK-cell homeostasis manifesting as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These immature NK-cell repertoires were characterized by expression of the proliferation/exhaustion markers Ki-67, Tim-3, and TIGIT and displayed blunted tumor target cell responses. Systems-level immune mapping revealed that the changes in immunophenotypes were confined to NK cells, leaving T-cell differentiation intact. RNA sequencing of NK cells from these patients showed upregulation of a network of genes, including TNFSF9, CENPF, MKI67, and TOP2A, associated with apoptosis and the cell cycle, but different from the conventional CD56bright signatures. Profiling of 249 plasma proteins showed a coordinated enrichment of pathways related to apoptosis and cell turnover, which correlated with immature NK-cell repertoires. Notably, most of these patients exhibited severe-grade neutropenia, suggesting that the profoundly altered NK-cell homeostasis was connected to the severity of their underlying etiology. Hence, although our data suggest that neutrophils are dispensable for NK-cell development and differentiation, some patients displayed a specific gap in the NK repertoire, associated with poor cytotoxic function and more severe disease manifestations.
piRNA-IPdb: a PIWI-bound piRNAs database to mining NGS sncRNA data and beyond
Authors: Barreñada Odei , Larriba Eduardo , Brieño-Enriquez Miguel A. , Mazo Jesús del 
Published: October 2021

Abstract
Background
PIWI-interacting RNAs (piRNAs) are an abundant single-stranded type of small non-coding RNAs (sncRNAs), which initially were discovered in gonadal cells, with a role as defenders of genomic integrity in the germline, acting against the transposable elements. With a regular size range of 21-35 nt, piRNAs are associated with a PIWI-clade of Argonaute family proteins. The most widely accepted mechanisms of biogenesis for piRNAs involve the transcription of longer precursors of RNAs to be processed, by complexes of proteins, to functional size, preferentially accommodating uridine residues at the 5’ end and 3’ methylation to increase the stability of these molecules. piRNAs have also been detected in somatic cells, with diverse potential functions, indicating their high plasticity and pleiotropic activity. Discovered about two decades ago, piRNAs are a large and versatile type of sncRNA and that remain insufficiently identified and analyzed, through next-generation sequencing (NGS), to evaluate their processing, functions, and biogenesis in different cell types and during development. piRNAs’ distinction from other sncRNAs has led to controversial results and interpretation difficulties when using existing databases because of the heterogeneity of the criteria used in making the distinction.

Description
We present “piRNA-IPdb”, a database based uniquely on datasets obtaining after the defining characteristic of piRNAs: those small RNAs bound to PIWI proteins. We selected and analyzed sequences from piRBase that exclusively cover the binding to PIWI. We pooled a total of 18,821,815 sequences from RNA-seq after immunoprecipitation that included the binding to any of the mouse PIWI proteins (MILI, MIWI, or MIWI2).

Conclusions
In summary, we present the characteristics and potential use of piRNA-IPdb database for the analysis of bona fide piRNAs.
Circadian miR-449c-5p regulates uterine Ca2+ transport during eggshell calcification in chickens
Authors: Cui Zhifu , Zhang Zhichao , Amevor Felix Kwame , Du Xiaxia , Li Liang , Tian Yaofu , Kang Xincheng , Shu Gang , Zhu Qing , Wang Yan , Li Diyan , Zhang Yao , Zhao Xiaoling 
Published: October 2021

Abstract
Background
miRNAs regulate circadian patterns by modulating the biological clocks of animals. In our previous study, we found that the clock gene exhibited a cosine expression pattern in the fallopian tube of chicken uterus. Clock-controlled miRNAs are present in mammals and Drosophila; however, whether there are clock-controlled miRNAs in the chicken uterus and, if so, how they regulate egg-laying rhythms is unclear. In this study, we selected 18 layer hens with similar ovipositional rhythmicity (each of three birds were sacrificed for study per 4 h throughout 24 h); their transcriptomes were scanned to identify the circadian miRNAs and to explore regulatory mechanisms within the uterus of chickens.

Results
We identified six circadian miRNAs that are mainly associated with several biological processes including ion trans-membrane transportation, response to calcium ion, and enrichment of calcium signaling pathways. Verification of the experimental results revealed that miR-449c-5p exhibited a cosine expression pattern in the chicken uterus. Ca2+-transporting ATPase 4 (ATP2B4) in the plasma membrane is the predicted target gene of circadian miR-449c-5p and is highly enriched in the calcium signaling pathway. We speculated that clock-controlled miR-449c-5p regulated Ca2+ transportation during eggshell calcification in the chicken uterus by targeting ATP2B4. ATP2B4 mRNA and protein were rhythmically expressed in the chicken uterus, and dual-luciferase reporter gene assays confirmed that ATP2B4 was directly targeted by miR-449c-5p. The expression of miR-449c-5p showed an opposite trend to that of ATP2B4 within a 24 h cycle in the chicken uterus; it inhibited mRNA and protein expression of ATP2B4 in the uterine tubular gland cells. In addition, overexpression of ATP2B4 significantly decreased intracellular Ca2+ concentration (P < 0.05), while knockdown of ATP2B4 accelerated intracellular Ca2+ concentrations. We found similar results after ATP2B4 knockdown by miR-449c-5p. Taken together, these results indicate that ATP2B4 promotes uterine Ca2+ trans-epithelial transport.

Conclusions
Clock-controlled miR-449c-5p regulates Ca2+ transport in the chicken uterus by targeting ATP2B4 during eggshell calcification.
“PrEP’s just to secure you like insurance”: a qualitative study on HIV pre-exposure prophylaxis (PrEP) adherence and retention among black cisgender women in Mississippi
Authors: Willie Tiara C. , Monger Mauda , Nunn Amy , Kershaw Trace , Stockman Jamila K. , Mayer Kenneth H. , Chan Philip A. , Adimora Adaora A. , Mena Leandro A. , Knight Deja , Philllips Karlye A. , Baral Stefan D. 
Published: October 2021

Abstract
Background
Pre-exposure prophylaxis (PrEP) has the potential to reduce transmission of HIV among Black cisgender women in the Southern United States (U.S.); however, national data suggests that PrEP initiation is lowest in the South and among Black women compared to other U.S. regions and white women. This study applied intersectionality and PrEP multilevel resilience frameworks to assess how socio-structural and clinical contexts shaped PrEP persistence among Black cisgender women in Mississippi.

Methods
Semi-structured interviews were conducted with eight Black cisgender women in Jackson, Mississippi. This sample was purposively recruited to include PrEP-initiated Black cisgender women.

Results
Six themes identified that shaped PrEP care among Black cisgender women: (1) internal assets, (2) sole responsibility to HIV prevention, (3) added protection in HIV serodifferent relationships, (4) financial issues, (5) trust and distrust in the medical system, and (6) side effects. Black cisgender women reported that PrEP persistence increased control over their sexual health, reduced anxiety about HIV, and promoted self-care. Black cisgender women also indicated that medication assistance programs increased PrEP affordability resulting in continued persistence.

Conclusions
In addition to preventing HIV, PrEP may yield secondary positive impacts on the health and relationships of Black cisgender women. However, very few Black cisgender women in the South are using PrEP given intersectional barriers and thus necessitates adaptive strategies to support PrEP initiation and persistence. Efforts aimed at increasing the coverage of PrEP among Black cisgender women should consider implementation strategies responsive to lived realities of Black women.
Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe
Authors: Robbins Tanya , Hanlon Charlotte , Kelly Ann H. , Gidiri Muchabayiwa Francis , Musiyiwa Mickias , Silverio Sergio A. , Shennan Andrew H. , Sandall Jane 
Published: October 2021

Abstract
Background
Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care.

Methods
We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model.

Results
Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy.

Conclusions
Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care.
Association between health locus of control and perceived stress in college student during the COVID-19 outbreak: a cross-sectional study in Iran
Authors: Ganjoo Mahasty , Farhadi Akram , Baghbani Reza , Daneshi Safieh , Nemati Reza 
Published: October 2021

Abstract
Background
The COVID-19 pandemic as a global mental health crisis has affected everyone, including students. The present study aimed to determine and investigate the relationship between health locus of control and perceived stress in students of Bushehr University of Medical Sciences (southern Iran) during the outbreak of COVID-19.

Methods
The present cross-sectional study examined 250 students of Bushehr University of Medical Sciences. We performed simple random sampling and utilized the demographic information form, Multidimensional Health Locus of Control scale (MHLCS) by Wallston, and Perceived Stress Scale (PSS) by Cohen to collect data. We analyzed data using the SPSS, Pearson correlation coefficient, and the hierarchical regression model with an error level of 5%.

Results
The mean perceived stress was 30.74 ± 8.09, and 92.4% of the students had moderate and high stress levels. Among the components of the health locus of control, the internal health locus of control (IHLC) had the highest mean in students (27.55 ± 3.81). Furthermore, the internal health locus of control (R = − 0.30, P < 0.001) had a significant inverse relationship, with perceived stress and the chance health locus of control (CHLC) (R = 0.30, P < 0.001) had a significant direct relationship. In the final regression model, the health locus of control and all the variables predicted 22.7% of the perceived stress variation in students during the COVID-19 period.

Conclusion
The results indicated that the internal health locus of control was associated with a reduction of perceived stress, and the powerful others health locus of control (PHLC) was related to its increase in students during the COVID-19 pandemic. Given the uncertain future, in the present work, universities are suggested to design web-based educational interventions alongside the curriculum to further strengthen the internal health locus of control and thus help reduce their perceived stress.
Impact of surgery on survival in breast cancer with bone metastases only: a SEER database retrospective analysis
Authors: Peng Pai , Chen Jiang-Yuan , Han Yun-Tao , Chen Xin , Li Hong-Yuan , Hu Chao-Hua , Wang Jin-Li 
Published: October 2021

Abstract
Background
It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis.

Methods
A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis.

Results
Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467–0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325–0.478, P < 0.001).

Conclusion
This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.
Knowledge, attitudes, and beliefs regarding molar incisor hypomineralisation amongst Swiss dental students
Authors: Hamza Blend , Elhennawy Karim , van Waes Hubertus , Papageorgiou Spyridon N. 
Published: October 2021

Abstract
Background
Knowledge obtained at the undergraduate level regarding molar incisor hypomineralisation (MIH) has an impact on future practice of dentists and paediatric dentists. This cross-sectional study aimed to assess final-year dental students’ knowledge, attitudes and beliefs towards MIH in all Swiss universities.

Methods
A previously utilised survey (in both English and German) was distributed among final-year dental students in all Swiss dental schools (Basel, Bern, Geneva and Zurich). It probed students’ knowledge, attitudes and beliefs regarding the diagnosis, prevalence, aetiology, and management of MIH, and was structured in two parts: knowledge/perception and clinical application. The students’ responses were analysed statistically with descriptive statistics.

Results
113 out of 133 final-year Swiss dental students took part in the study (85%). Nearly all students were familiar with MIH (99%), but only 12% of them felt confident when diagnosing MIH clinically. Direct composite fillings (66%), indirect restorations (28%) and preformed stainless-steel crowns (26%) were chosen as most suitable treatment options for MIH-affected teeth.

Conclusion
Final-year Swiss dental students are well informed about MIH. However, they report low level of confidence when clinically confronted with MIH-affected teeth regarding its diagnosis and treatment. Swiss Universities curricula should be revisited accordingly.
Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages
Authors: Sayre Dean , Steinhardt Laura C. , Irinantenaina Judickaelle , Dentinger Catherine , Rasoanaivo Tsinjo Fehizoro , Kapesa Laurent , Razafindrakoto Jocelyn , Legrand Agathe , Prada Nicole , Gutman Julie , Lewis Lauren , Mangahasimbola Reziky Tiandraza , Andriamananjara Mauricette , Ravaoarinosy Aimée Vololoniala , Ralemary Nicolas , Garchitorena Andres , Harimanana Aina 
Published: October 2021

Abstract
Background
Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours.

Methods
Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns.

Results
Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5–29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5–14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5–14-year-olds reported fever in the two weeks prior to survey (p = 0.044).

Conclusions
The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.
CircRNF220, not its linear cognate gene RNF220, regulates cell growth and is associated with relapse in pediatric acute myeloid leukemia
Authors: Liu Xiaodan , Liu Xiaoping , Cai Mansi , Luo Ailing , He Yingyi , Liu Sha , Zhang Xiaohong , Yang Xu , Xu Ling , Jiang Hua 
Published: October 2021

Abstract
Background
Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and have been confirmed to be critical in tumorigenesis and to be potential biomarkers or therapeutic targets. However, only a few circRNAs have been functionally characterized in pediatric acute myeloid leukemia (AML).

Methods
Here, we investigated the expression pattern of circRNAs in pediatric AML using a circRNA microarray. The characteristics, potential diagnostic value, and prognostic significance of circRNF220 were evaluated. A series of functional experiments were performed to investigate the role of circRNF220 in primary pediatric AML cells. Then we investigated the aberrant transcriptional networks regulated by circRNF220 in primary AML cells by RNA-seq. Furthermore, biotin RNA pulldown assays were implemented to verify the relationship between circRNF220 and miR-30a.

Results
We identified a circRNA, circRNF220, which was specifically abundant in and accumulated in the peripheral blood and bone marrow of pediatric patients with AML. It could distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity. Significantly, circRNF220 expression independently predicted prognosis, while high expression of circRNF220 was an unfavorable prognostic marker for relapse. Furthermore, we characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibited proliferation and promoted apoptosis in AML cell lines and primary cells. Mechanistically, circRNF220 may act as an endogenous sponge of miR-30a to sequester miR-30a and inhibit its activity, which increases the expression of its targets MYSM1 and IER2 and implicated in AML relapse.

Conclusions
Collectively, these findings demonstrated that circRNF220 could be highly efficient and specific for the accurate diagnosis of pediatric AML, with implications for relapse prediction.