bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct reinforcement learning profiles distinguish between language and attentional neurodevelopmental disorders
Authors: Nissan Noyli , Hertz Uri , Shahar Nitzan , Gabay Yafit 
Published: March 2023

Abstract
Background
Theoretical models posit abnormalities in cortico-striatal pathways in two of the most common neurodevelopmental disorders (Developmental dyslexia, DD, and Attention deficit hyperactive disorder, ADHD), but it is still unclear what distinct cortico-striatal dysfunction might distinguish language disorders from others that exhibit very different symptomatology. Although impairments in tasks that depend on the cortico-striatal network, including reinforcement learning (RL), have been implicated in both disorders, there has been little attempt to dissociate between different types of RL or to compare learning processes in these two types of disorders. The present study builds upon prior research indicating the existence of two learning manifestations of RL and evaluates whether these processes can be differentiated in language and attention deficit disorders. We used a two-step RL task shown to dissociate model-based from model-free learning in human learners.

Results
Our results show that, relative to neurotypicals, DD individuals showed an impairment in model-free but not in model-based learning, whereas in ADHD the ability to use both model-free and model-based learning strategies was significantly compromised.

Conclusions
Thus, learning impairments in DD may be linked to a selective deficit in the ability to form action-outcome associations based on previous history, whereas in ADHD some learning deficits may be related to an incapacity to pursue rewards based on the tasks' structure. Our results indicate how different patterns of learning deficits may underlie different disorders, and how computation-minded experimental approaches can differentiate between them.
B7-H3 expression is associated with high PD-L1 expression in clear cell renal cell carcinoma and predicts poor prognosis
Authors: Lee Jung Hee , Kim Yong Jun , Ryu Hyun Woo , Shin Seung Won , Kim Eun Ji , Shin So Hyun , Park Joon Young , Kim So Young , Hwang Chung Su , Na Joo-Young , Shin Dong Hoon , Kim Jee Yeon , Lee Hyun Jung 
Published: March 2023

Abstract
Background
Clear cell Renal cell carcinoma (ccRCC) is an immunogenic tumor. B7 family members, such as CTLA-4, PD-1, and PD-L1, are the main components of immune checkpoints that regulate various immune responses. Specifically, B7-H3 regulates T cell-mediated immune responses against cancer. This study aimed to analyze the association between B7-H3 and CTLA-4 expression and the prognostic factors of ccRCC to provide a basis for their potential use as predictive factors and in immunotherapy.

Methods
Formalin-fixed paraffin-embedded specimens were obtained from 244 ccRCC patients, and B7-H3, CTLA-4, and PD-L1 expressions were evaluated using immunohistochemical staining.

Results
B7-H3 and CTLA-4 were positive in 73 (29.9%) and 57 (23.4%) of the 244 patients, respectively. B7-H3 expression was significantly associated with PD-L1 expression (P <  0.0001); however, CTLA-4 expression was not (P = 0.842). Kaplan–Meier analysis showed that positive B7-H3 expression was associated with poor progression-free survival (PFS) (P <  0.0001), whereas CTLA-4 expression was not (P = 0.457). Multivariate analysis revealed that B7-H3 was correlated with poor PFS (P = 0.031), whereas CTLA-4 was not (P = 0.173).

Conclusions
To the best of our knowledge, this study is the first to investigate B7-H3 and PD-L1 expression and survival in ccRCC. B7-H3 expression is an independent prognostic factor for ccRCC. Furthermore, multiple immune cell inhibitory targets, such as B7-H3 and PD-L1, can be used for therapeutic tumor regression in a clinical setting.
Breastfeeding among South Sudanese refugees in protracted settlements in Adjumani district, Uganda: facilitators and barriers
Authors: Walters Christine N. , Rakotomanana Hasina , Komakech Joel J. , Kabahenda Margaret , Joyce Jillian M. , Hildebrand Deana A. , Ciciolla Lucia , Stoecker Barbara J. 
Published: March 2023

Abstract
Background
Evidence suggests that forced migration and refugee status may adversely impact mothers’ breastfeeding choices. Furthermore, suboptimal breastfeeding practices have been reported among vulnerable populations including those living in refugee settlements. Therefore, this study investigated the barriers and facilitators of breastfeeding in protracted settlements in Adjumani district, in the West Nile region in Uganda.

Methods
This study was conducted among refugees living in protracted settlements located in Uganda in July 2019. Participants, originally from South Sudan, included mothers (n = 63) and fathers (n = 32) of children less than 24 months of age. Agojo, Ayilo-I, and Nyumanzi were randomly selected among the 17 refugee settlements in Adjumani. Participants formed a total of six focus group discussions (FGDs); four FGDs for mothers and two FGDs for fathers. Each FGD consisted of 15–16 participants. Data were transcribed verbatim and back-translated into English. Thematic analysis was used and data were analyzed using NVivo, v. 12.

Results
Facilitators of breastfeeding included knowledge of breastfeeding benefits, support from husband/father, support from the community, and support from non-governmental organizations. Mothers and fathers noted that breastfeeding protected children from diseases and breastfed children grew well. Fathers, the community, and organizations provided material support for breastfeeding mothers. Four themes were identified as barriers to breastfeeding: physical, socioeconomic, knowledge, and psychosocial. Mothers and fathers described physical barriers such as mothers stop breastfeeding when they are sick or they feel they are not producing enough breastmilk. Mothers reported that working or educated mothers may use other milk to feed their infant. Some mothers and fathers believed infants under six months needed more than breastmilk. Fathers described psychosocial barriers such as mothers’ fear of pain during breastfeeding and maternal mental health issues.

Conclusion
Interventions and policies that aim to improve breastfeeding in protracted settlements should consider addressing the barriers to breastfeeding at each level: physical, socioeconomic, knowledge, and psychosocial. Involving and encouraging support from husbands/fathers, relatives, and the community may increase adherence to breastfeeding recommendations.
The infant feeding methods promoted by South African Instagram influencers in relation to crying and sleeping, 2018–2020: a retrospective digital ethnography
Authors: Pilime Sukoluhle , Jewett Sara 
Published: March 2023

AbstractBackgroundGlobally, there has been a decline in breastfeeding rates. This has resulted in increased infant mortality due to infectious diseases and inappropriate feeding practices. The aggressive marketing of breastmilk substitutes (BMS) by manufacturers has contributed, in part, to these declines. With the progressive use of social media, marketing has shifted from traditional methods to the use of influencers, who command a huge following on their social media accounts and influence the daily decisions of their followers. This study investigates the infant feeding methods and associated products promoted by South African influencers in relation to crying and sleeping and their followers’ responses.MethodsThis was a retrospective study, which used a mixed methods digital ethnographic approach to analyse posts related to infant feeding methods that were made by seven South African Instagram influencers between the period of January 2018 to December 2020. Framing analysis was used to analyse qualitative data and quantitative data were analysed descriptively.ResultsFrom the 62 posts that were analysed, 27 were sponsored advertisements (some violating local regulations) and 35 posts promoted breastfeeding. The 18,333 follower comments and 918,299 likes in response to the posts were also analysed. We found that influencers presented BMS products as a solution for a child who cries a lot and has trouble sleeping. BMS were framed as helpful for children who are seemingly always hungry and dissatisfied with breastmilk alone. The study also found that some influencers promoted breastfeeding on their Instagram pages. Unlike BMS posts, breastfeeding posts were not sponsored. With a few exceptions, followers tended to support and reinforce the framing of influencers.ConclusionStiffer regulations should be enforced against companies using influencers to promote infant formula and other BMS products, with proactive monitoring of social media. Professionals giving advice contrary to the guidelines from the WHO should be reported according to Regulation 991 and made accountable. Proactive engagement with Instagram influencers to promote breastfeeding should be considered.
Corn360: a method for quantification of corn kernels
Authors: Gillette Samantha , Yin Lu , Kianian Penny M. A. , Pawlowski Wojciech P. , Chen Changbin 
Published: March 2023

Abstract
Background
The rapidly advancing corn breeding field calls for high-throughput methods to phenotype corn kernel traits to estimate yield and to study their genetic inheritance. Most of the existing methods are reliant on sophisticated setup, expertise in statistical models and programming skills for image capturing and analysis.

Results
We demonstrated a portable, easily accessible, affordable, panoramic imaging capturing system called Corn360, followed by image analysis using freely available software, to characterize total kernel count and different patterned kernel counts of a corn ear. The software we used did not require programming skills and utilized Artificial Intelligence to train a model and to segment the images of mixed patterned corn ears. For homogeneously patterned corn ears, our results showed accuracies of 93.7% of total kernel count compared to manual counting. Our method allowed to save an average of 3 min 40 s per image. For mixed patterned corn ears, our results showed accuracies of 84.8% or 61.8% of segmented kernel counts. Our method has the potential to greatly decrease counting time per image as the number of images increases. We also demonstrated a case of using Corn360 to count different categories of kernels on a mixed patterned corn ear resulting from a cross of sweet corn and sticky corn and showed that starch:sweet:sticky segregated in a 9:4:3 ratio in its F2 population.

Conclusions
The panoramic Corn360 approach enables for a portable low-cost high-throughput kernel quantification. This includes total kernel quantification and quantification of different patterned kernels. This can allow for quick estimate of yield component and for categorization of different patterned kernels to study the inheritance of genes controlling color and texture. We demonstrated that using the samples resulting from a sweet × sticky cross, the starchiness, sweetness and stickiness in this case were controlled by two genes with epistatic effects. Our achieved results indicate Corn360 can be used to effectively quantify corn kernels in a portable and cost-efficient way that is easily accessible with or without programming skills.
Transmembrane potential, an indicator in situ reporting cellular senescence and stress response in plant tissues
Authors: Liu Hai , Li Yufei , Peng Ting , Xue Shaowu 
Published: March 2023

AbstractBackgroundPlant cells usually sustain a stable membrane potential due to influx and/or efflux of charged ions across plasma membrane. With the growth and development of plants, different tissues and cells undergo systemic or local programmed decline. Whether the membrane potential of plasma membrane could report senescence signal of plant tissues and cells is unclear.ResultsWe applied a maneuverable transmembrane potential (TMP) detection method with patch-clamp setup to examine the senescence signal of leaf tissue cells in situ over the whole life cycle inArabidopsis thaliana. The data showed that the TMPs of plant tissues and cells were varied at different growth stages, and the change of TMP was higher at the vegetative growth stage than at the reproductive stage of plant growth. The distinct change of TMP was detectable between the normal and the senescent tissues and cells in several plant species. Moreover, diverse abiotic stimuli, such as heat stress, hyperpolarized the TMP in a short time, followed by depolarized membrane potential with the senescence occurring. We further examined the TMP of plant chloroplasts, which also indicates the senescence signal in organelles.ConclusionsThis convenient TMP detection method can report the senescence signal of plant tissues and cells, and can also indicate the potential of plant tolerance to environmental stress.
Comparison of long-term outcomes of stereotactic body radiotherapy (SBRT) via Helical tomotherapy for early-stage lung cancer with or without pathological proof
Authors: Fan Shaonan , Zhang Qi , Chen Jingyao , Chen Gang , Zhu Jiangyi , Li Tingting , Xiao Han , Du Shisuo , Zeng Zhaochong , He Jian 
Published: March 2023

AbstractBackgroundStereotactic body radio therapy (SBRT) has emerged as a standard treatment option for nonsurgical candidates with early-stage non-small cell lung cancer (NSCLC). Pathological proof is sometimes difficult to obtain in patients with solitary pulmonary nodules (SPNs). We aimed to compare the clinical outcomes of stereotactic body radiotherapy via helical tomotherapy (HT-SBRT) for early-stage lung cancer patients with or without a pathological diagnosis.MethodsBetween June 2011 and December 2016, we treated 119 lung cancer patients with HT-SBRT, including 55 with a clinical diagnosis and 64 with a pathological diagnosis. Survival outcomes, including local control (LC), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared between two cohorts with and without a pathological diagnosis.ResultsThe median follow-up for the whole group was 69 months. Patients with a clinical diagnosis were significantly older (p = 0.002). No significant differences were observed between the clinical and pathological diagnosis cohorts in terms of the long-term outcome, with 5-year LC, PFS, CSS, and OS of 87% versus 83% (p = 0.58), 48% versus 45% (p = 0.82), 87% versus 84% (p = 0.65), and 60% versus 63% (p = 0.79), respectively. Recurrence patterns and toxicity were also similar.ConclusionsEmpiric SBRT appears to be a safe and effective treatment option in a multidisciplinary setting when patients with SPNs highly suggestive of malignancy are unable/refuse to obtain a definitive pathological diagnosis.
Safety and efficacy of single insertion accelerated MR-image guided brachytherapy following chemo–radiation in locally advanced cervix cancer: modifying our EMBRACE during the COVID pandemic
Authors: Stevens Mark J. , Ko Florence , Martland Judith , Brown Ryan , Bell Linda , Atyeo John , Yim Jackie 
Published: March 2023

Abstract
Background
Utero-vaginal brachytherapy (BT) is an irreplaceable care component for the curative treatment of locally advanced cervix cancer (LACC). Magnetic Resonance Imaging (MRI)-image guided adaptive BT (IGABT) using the GYN-GEC-ESTRO EMBRACE guidelines is the international care standard. Usually following chemo–radiation therapy (CRT), IGABT has high proven utility in LACC but requires significant health system resources. Timely access was disrupted by the COVID-19 pandemic which challenged us to re-design our established IGABT care pathway.

Methods
From April 2020 consecutive patients with LACC were enrolled after CRT in a single arm exploratory non-inferiority study of a modified IGABT (mIGABT) protocol. This delivered an iso-effective IGABT dose (39.3 Gy: EQD2: α/β10Gy concept) over a 24-h period during a single overnight hospitalisation.

Results
Fourteen LACC patients received mIGABT from April 2020 to March 2022. Median age was 62.5 years (37–82 years). LACC histology was primary squamous (9/14) or adeno-carcinoma (5/14). International Federation of Gynaecology and Obstetrics (FIGO) 2018 stages ranged from IB1/2 (N = 3), IIA1/IIB (5), IIIB (2), IIIC1/2 (4) with mean ± standard deviation (SD) gross tumour volume-at-diagnosis (GTV_D) of 37.7 cc ± 71.6 cc. All patients achieved complete metabolic, clinical, and cytologic cancer response with CRT and IGABT. High-risk HPV was cleared by 6-months. Complete MRI-defined cancer response before mIGABT (GTV_Fx1) was seen in 77% of cases (10/13). Only two women developed metastatic disease and one died at 12-months; 13 patients were alive without cancer at mean 20.3 ± 7.2 months follow-up. Actuarial 2-year overall survival was 93%. Compared with our pre-COVID IGABT program, overall mIGABT cost-saving in this cohort was USD 22,866. Prescribed dose covered at least 90% (D90) of the entire cervix and any residual cancer at time of BT (HRCTV_D90: high-risk clinical target volume) with 3-fractions of 8.5 Gy delivered over 24-h (22.8 ± 1.7 h). Total treatment time including CRT was 38 days. The mIGABT schedule was well tolerated and the entire cohort met EMBRACE recommended (EQD2: α/β10Gy) combined HRCTV_D90 coverage of 87.5 ± 3.7 Gy. Similarly, organ-at-risk (OAR) median: interquartile range D2cc constraints (EQD2: α/β3Gy) were EMBRACE compliant: bladder (65.9 Gy: 58.4–72.5 Gy), rectum (59.1 Gy: 55.7–61.8 Gy), and sigmoid colon (54.6 Gy: 50.3–58.9 Gy). ICRU recto-vaginal point dose was significantly higher (75.7 Gy) in our only case of severe (G4) pelvic toxicity.

Conclusions
This study demonstrated the utility of mIGABT and VMAT CRT in a small cohort with LACC. Loco-regional control was achieved in all cases with minimal emergent toxicity. Single insertion mIGABT was logistically efficient, cost-saving, and patient-centric during the COVID-19 pandemic.
Systematic in vitro analysis of therapy resistance in glioblastoma cell lines by integration of clonogenic survival data with multi-level molecular data
Authors: Schnöller Leon Emanuel , Piehlmaier Daniel , Weber Peter , Brix Nikko , Fleischmann Daniel Felix , Nieto Alexander Edward , Selmansberger Martin , Heider Theresa , Hess Julia , Niyazi Maximilian , Belka Claus , Lauber Kirsten , Unger Kristian , Orth Michael 
Published: March 2023

AbstractDespite intensive basic scientific, translational, and clinical efforts in the last decades, glioblastoma remains a devastating disease with a highly dismal prognosis. Apart from the implementation of temozolomide into the clinical routine, novel treatment approaches have largely failed, emphasizing the need for systematic examination of glioblastoma therapy resistance in order to identify major drivers and thus, potential vulnerabilities for therapeutic intervention. Recently, we provided proof-of-concept for the systematic identification of combined modality radiochemotherapy treatment vulnerabilities via integration of clonogenic survival data upon radio(chemo)therapy with low-density transcriptomic profiling data in a panel of established human glioblastoma cell lines. Here, we expand this approach to multiple molecular levels, including genomic copy number, spectral karyotyping, DNA methylation, and transcriptome data. Correlation of transcriptome data with inherent therapy resistance on the single gene level yielded several candidates that were so far underappreciated in this context and for which clinically approved drugs are readily available, such as the androgen receptor (AR). Gene set enrichment analyses confirmed these results, and identified additional gene sets, including reactive oxygen species detoxification, mammalian target of rapamycin complex 1 (MTORC1) signaling, and ferroptosis/autophagy-related regulatory circuits to be associated with inherent therapy resistance in glioblastoma cells. To identify pharmacologically accessible genes within those gene sets, leading edge analyses were performed yielding candidates with functions in thioredoxin/peroxiredoxin metabolism, glutathione synthesis, chaperoning of proteins, prolyl hydroxylation, proteasome function, and DNA synthesis/repair. Our study thus confirms previously nominated targets for mechanism-based multi-modal glioblastoma therapy, provides proof-of-concept for this workflow of multi-level data integration, and identifies novel candidates for which pharmacological inhibitors are readily available and whose targeting in combination with radio(chemo)therapy deserves further examination. In addition, our study also reveals that the presented workflow requires mRNA expression data, rather than genomic copy number or DNA methylation data, since no stringent correlation between these data levels could be observed. Finally, the data sets generated in the present study, including functional and multi-level molecular data of commonly used glioblastoma cell lines, represent a valuable toolbox for other researchers in the field of glioblastoma therapy resistance.
Metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway in osteoarthritis
Authors: Yan Shiju , Dong Wenjing , Li Zhirui , Wei Junqiang , Han Tao , Wang Junliang , Lin Feng 
Published: March 2023

Abstract
Background
Osteoarthritis (OA) is the most common degenerative disease in joints among elderly patients. Senescence is deeply involved in the pathogenesis of osteoarthritis. Metformin is widely used as the first-line drug for Type 2 diabetes mellitus (T2DM), and has great potential for the treatment of other aging-related disorders, including OA. However, the role of metformin in OA is not fully elucidated. Therefore, our aim here was to investigate the effects of metformin on human chondrocytes.

Methods
After metformin treatment, expression level of microRNA-34a and SIRT1 in chondrocyte were detected with quantitative real-time PCR and immunofluorescence staining. Then, microRNA-34a mimic and small interfering RNA (siRNA) against SIRT1 (siRNA-SIRT1) were transfected into chondrocyte. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to assess chondrocyte senescence. Chondrocyte viability was illustrated with MTT and colony formation assays. Western blot was conducted to detect the expression of P16, IL-6, matrix metalloproteinase-13 (MMP-13), Collagen type II (COL2A1) and Aggrecan (ACAN).

Results
We found that metformin treatment (1 mM) inhibited microRNA-34a while promoted SIRT1 expression in OA chondrocytes. Both miR-34a mimics and siRNA against SIRT1 inhibited SIRT1 expression in chondrocytes. SA-β-gal staining assay confirmed that metformin reduced SA-β-gal-positive rate of chondrocytes, while transfection with miR-34a mimics or siRNA-SIRT1 reversed it. MTT assay and colony formation assay showed that metformin accelerated chondrocyte proliferation, while miR-34a mimics or siRNA-SIRT1 weakened this effect. Furthermore, results from western blot demonstrated that metformin suppressed expression of senescence-associated protein P16, proinflammatory cytokine IL-6 and catabolic gene MMP-13 while elevated expression of anabolic proteins such as Collagen type II and Aggrecan, which could be attenuated by transfection with miR-34a mimics.

Conclusion
Overall, our data suggest that metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway, indicating it could be a novel strategy for OA treatment.