bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supplemental Table S7 from Real-world Validation of TMB and Microsatellite Instability as Predictive Biomarkers of Immune Checkpoint Inhibitor Effectiveness in Advanced Gastroesophageal Cancer
Authors: Graf Ryon P. , Fisher Virginia , Creeden James , Schrock Alexa B. , Ross Jeffrey S. , Nimeiri Halla , Oxnard Geoffrey R. , Klempner Samuel J. 
Published: April 2023

<p>Restricted Mean Survival Time Difference by TMB Status in the 2L and 1L Comparative Effectiveness Cohorts. Conditional average treatment effects are defined in each TMB subgroup as the difference in expected survival time up to 3 years when treated with ICPI vs chemo. For instance, within the 1st 3 years after 2nd line treatment initiation, patients with TMB10+ would be expected to have a mean of 15.4 more months until treatment switching on ICPI compared to chemo. Bootstrap 95% confidence intervals (q025, q975) were estimated with 5000 resampling replicates.</p>
Status of the Implementation of Alternative Learning System in Jalajala Elementary School
Authors: Besmonte Ederlinda SJ. 
Published: April 2023

The study aimed to assess the status of the implementation of Alternative Learning System (ALS) in Jalajala Elementary School during the School Year 2021-2022. The study considered 148 ALS learners in the said school. Purposive sampling technique was used. The respondents were described in terms of their age, sex, civil status, educational attainment, and monthly family income. Descriptive survey research design was used. A researcher-made questionnaire-checklist was utilized to assess the implementation of Alternative Learning System (ALS) in public elementary schools with respect to teaching methodologies, instructional materials, and evaluative techniques. Problems encountered in the status of the implementation of Alternative Learning System were also determined.
The study revealed that the ALS learners are mostly on their maturity ages and predominantly males. Most of them are single; have monthly income below Php 10,000 and mostly are high school undergraduates and elementary undergraduates. Alternative Learning System is often implemented with respect to teaching methodologies, instructional materials and evaluative techniques as evaluated by ALS learners. No significant difference exists on the perception of the respondents on the implementation of Alternative Learning System with respect to teaching methodologies, instructional materials, and evaluative techniques in terms of age, sex, civil status, educational attainment, and monthly family income. The most common problems encountered by ALS learners on the implementation of Alternative Learning System are family problems, marital problem, and school too far from home and financial problem as well.
Some of the recommendations include continuous implementation of the programs in ALS, provision of better co-curricular programs, purchasing of needed facilities and equipment, and provision of opportunities to ALS graduates.
An Unbeliever Can Rule Dār al-Islām: Ḥanafī Law in the Wake of the Mongol Invasion
Authors: Chen Edith X. 
Published: April 2023

Abstract
Prior to the Mongol invasion of Iran in the 7th/13th century, Ḥanafī jurists had adopted two definitions of Islamic lands (dār al-islām): according to a “lenient” definition attributed to Abū Ḥanīfa, an unbelieving ruler may rule over dār al-islām, and according to a “strict” definition attributed to Abū Yūsuf and al-Shaybānī, he may not. As the Mongols overran Central Asia and Iran, later Ḥanafīs began to favor the lenient definition so that lands under non-Muslim occupation might retain the status of dār al-islām as long as Muslims had security and the freedom to worship. In this article, I evaluate the assumptions about Mongol rule that underpin the lenient definition. Persian historians such as Waṣṣāf and Shabānkāraʾī report that the Mongols permitted self-rule, and Muslims were adjudicated in their own courts according to Islamic law. Local histories support the claim that Islamic life can continue under occupation by nonbelievers.
Ovid and Petronius’ Pyramus and Thisbe (Satyricon 131.8-11 and Metamorphoses 4.55-166)
Authors: Agócs Peter , Lightfoot Jessica 
Published: April 2023

Abstract
Petronius’ engagement with Ovid’s poetry in the Croton episode of the Satyricon is more extensive than has previously been appreciated. As well as drawing upon Ovidian elegiac poetry, especially Amores 3.7, the description of Encolpius’ second failed tryst with Circe at Satyricon 131.8-11 also alludes to Ovid’s narrative of Pyramus and Thisbe at Metamorphoses 4.55-166. This ironic perversion of one of the Metamorphoses’ most innocent and tragic narratives parallels Petronius’ later Ovidian allusion at 135.3-137.12, where the story of the pious couple Philemon and Baucis (Met. 8.616-724) is recalled during Encolpius’ visit to Oenothea’s hut. Petronius’ engagement with the Metamorphoses during Encolpius’ exploits in Croton is thus shown to be deeper than has previously been realised.
Evaluation of Graft Ligamentization by MRI After Anterior Cruciate Ligament Reconstruction
Authors: Yau W.P. , Chan Yat-Chi 
Published: April 2023

Background: The tendon graft used in anterior cruciate ligament reconstruction (ACLR) undergoes “ligamentization” after implantation, and the reported length of this process varies from 6 to 48 months. Some grafts have ruptured at subsequent follow-up evaluations. Although the progress of graft ligamentization can be followed with postoperative magnetic resonance imaging (MRI) for reassessment, it is not known whether a delay in ligamentization (as reflected by a higher signal of the graft) is associated with an increased chance of subsequent graft rupture. Hypothesis: Signal intensity of the graft on reassessment MRI (signal-noise quotient [SNQ]) would be associated with the incidence of future graft rupture at subsequent follow-up. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 565 ACLRs with intact graft on first-time reassessment MRI after surgery were followed for a mean period of 67 months. The rates of 1-year and 2-year follow-up were 99.5% and 84.5%, respectively. The signal intensity of the intact graft on the first-time reassessment MRI was evaluated (1) quantitatively by the SNQ and (2) qualitatively with the modified Ahn classification. Among the 565 ACLRs, 23 additional graft ruptures developed during a time interval of 7 months to 9 years after the surgery. Results: Higher SNQ was associated with increased chance of subsequent graft rupture (SNQ 7.3 ± 6 for subsequent graft rupture vs 4.4 ± 4 for grafts without subsequent rupture; P = .004, Mann-Whitney U test). The other important confounders that were associated with increased chance of graft rupture were younger age at the time of ACLR ( P < .001) and longer follow-up time ( P = .002). Multiple linear regression showed that all 3 factors (higher SNQ, younger age, and longer follow-up) were independent predictors of graft rupture (SNQ, P = .03; age, P < .001; follow-up, P = .012). When the reassessment MRI was performed in the second year after ACLR, the odds ratio of future graft rupture of a heterogeneous hyperintense graft when compared with a homogeneous hypointense graft was 12.1 (95% CI = 2.8 to 52.6) P < .001, Fisher exact test). Conclusion: Higher signal intensity of the intact graft on reassessment MRI (higher SNQ and heterogeneous hyperintense graft) was associated with increased chance of subsequent graft rupture.
Genome-wide identification of WD40 transcription factors and their regulation of the MYB-bHLH-WD40 (MBW) complex related to anthocyanin synthesis in Qingke (Hordeum vulgare L. var. nudum Hook. f.)
Authors: Chen Lin , Cui Yongmei , Yao Youhua , An Likun , Bai Yixiong , Li Xin , Yao Xiaohua , Wu Kunlun 
Published: April 2023

Abstract
Background
WD40 transcription factors, a large gene family in eukaryotes, are involved in a variety of growth regulation and development pathways. WD40 plays an important role in the formation of MYB-bHLH-WD (MBW) complexes associated with anthocyanin synthesis, but studies of Qingke barley are lacking.

Results
In this study, 164 barley HvWD40 genes were identified in the barley genome and were analyzed to determine their relevant bioinformatics. The 164 HvWD40 were classified into 11 clusters and 14 subfamilies based on their structural and phylogenetic protein profiles. Co-lineage analysis revealed that there were 43 pairs between barley and rice, and 56 pairs between barley and maize. Gene ontology (GO) enrichment analysis revealed that the molecular function, biological process, and cell composition were enriched. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the RNA transport pathway was mainly enriched. Based on the identification and analysis of the barley WD40 family and the transcriptome sequencing (RNA-seq) results, we found that HvWD40-140 (WD40 family; Gene ID: r1G058730), HvANT1 (MYB family; Gene ID: HORVU7Hr1G034630), and HvANT2 (bHLH family; Gene ID: HORVU2Hr1G096810) were important components of the MBW complex related to anthocyanin biosynthesis in Qingke, which was verified via quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), subcellular location, yeast two-hybrid (Y2H), and bimolecular fluorescent complimentary (BiFC) and dual-luciferase assay analyses.

Conclusions
In this study, we identified 164 HvWD40 genes in barley and found that HvnANT1, HvnANT2, and HvWD40-140 can form an MBW complex and regulate the transcriptional activation of the anthocyanin synthesis related structural gene HvDFR. The results of this study provide a theoretical basis for further study of the mechanism of HvWD40-140 in the MBW complex related to anthocyanin synthesis in Qingke.
The effect of biological agent on body composition in patients with Crohn’s disease
Authors: Choi Eun Jeong , Baek Dong Hoon , Lee Hong Sub , Song Geun Am , Kim Tae Oh , Park Yong Eun , Lee Chang Min ,   Busan Ulsan Gyeongnam Intestinal Study Group Society (BIGS), Lee Jong Hoon 
Published: April 2023

Abstract
Background
Crohn’s disease (CD) is associated with altered body composition, affecting clinical outcomes. We evaluated the impact of biologics on body composition in CD patients.

Methods
This multicenter longitudinal study across four Korean university hospitals conducted from January 2009 to August 2021 retrospectively reviewed data of CD patients with abdominal computed tomography (CT) before and after the biologic treatment. Skeletal muscle area (SMA), visceral fat area (VFA), and subcutaneous fat area (SFA) of the third lumbar vertebra (L3) on CT were measured. Myopenia was defined as L3 skeletal muscle index (SMI) of < 49 and < 31 cm2/m2 for men and women, respectively.

Results
Among 112 participants, 79 (70.5%) had myopenia. In the myopenia group, all body composition parameters were significantly increased after the biologic treatment: SMI (37.68 vs. 39.40 cm2/m2; P < 0.001), VFA (26.12 vs. 54.61 cm2; P < 0.001), SFA (44.29 vs. 82.42 cm2; P < 0.001), while no significant differences were observed in the non-myopenia group. In multivariate analysis, penetrating CD (hazard ratio, 5.40; P = 0.020) was the independent prognostic factor for surgery. Operation-free survival rate tended to decrease in the myopenia group (Log-rank test, P = 0.090).

Conclusions
Biological agents can increase all body composition parameters in CD patients with myopenia. These patients are more likely to experience surgery.
Disparities in oesophageal cancer risk by age, sex, and nativity in Kuwait:1980–2019
Authors: Akhtar Saeed , Al-Shammari Ahmad , Al-Huraiti Mohammad , Al-Anjery Fouzan , Al-Sabah Salman , Memon Anjum , Siddique Iqbal 
Published: April 2023

Abstract
Background
This cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980–2019.

Methods
Using oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model.

Results
Overall ASIR of oesophageal cancer was 10.51 (95% CI: 6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer. Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly (p < 0.005) declined in subsequent periods till 2015-19.

Conclusions
A high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.
Spatial distribution and determinants of stunting, wasting and underweight in children under-five in Ethiopia
Authors: Kuse Kenenisa Abdisa , Debeko Dereje Danbe 
Published: April 2023

AbstractBackgroundThe burden of malnutrition in children under five remains an important child health issue where significant regional variations are observed in Ethiopia. The main aim of the current study was to explore the spatial distribution of stunting, wasting, and underweight in children under five in Ethiopia.MethodsThe secondary data from EDHS, 2016, was employed, and a total of 7960 under-five children were included in the analysis. The general spatial analysis was performed to explore the spatial distribution of malnutrition among under-five within and between the regions of Ethiopia. The Spatial Lag and Spatial Error models were used to examine the spatial dependence between stunting, wasting, and being underweight. The Geographically weighted regression analysis was performed to estimate the types and strength of relationships between malnutrition and associated determinant factors across the regions and within the clusters or Zones of each region.ResultsAmong the under-five children included in the study, 36.6% were stunted, 12.2% were wasted and 25.2% were underweight. The Global Moran Index's value indicates (Stunting, I = 0.3135,p-value < 0.00001, Wasting, I = 0.1948,p-value < 0.0001 and Underweight, I = 0.5291,p-value < 0.0001) that there was a significant spatial variation of malnutrition across the regions and Zones of Ethiopia. The significant source of spatial variation of malnutrition in children under five was associated with the mother's education level, drinking water facility, toilet facilities, number of children under-five in the household, household’s wealth index, breastfeeding duration of the child, child size at birth, Body Mass Index of Mothers (BMI), region, and place of residence.ConclusionsThe spatial association and spatial patterns of stunting, wasting, and being underweight were clustered within and between the regions of Ethiopia. The hotspot areas of stunting, wasting, and being underweight were detected in the regions where there were poor health facilities and limited socioeconomic indicators.
An open-label randomised controlled trial evaluating the efficacy of a meningococcal serogroup B (4CMenB) vaccine on Neisseria gonorrhoeae infection in gay and bisexual men: the MenGO study protocol
Authors: Thng Caroline , Semchenko Evgeny A. , Hughes Ian , O’Sullivan Maree , Seib Kate L. 
Published: April 2023

Abstract
Background
Gonorrhoea is an ongoing public health concern due to its rising incidence and the emergence of antibiotic resistance. There are an estimated 82 million new Neisseria gonorrhoeae infections each year, with several populations at higher risk for gonococcal infection, including gay and bisexual men (GBM). If left untreated, infection can lead to serious morbidity including infertility, sepsis and increased risk of HIV acquisition. Development of a gonorrhoea vaccine has been challenging, however there is observational evidence that serogroup B meningococcal vaccines, used to protect against the closely related bacteria Neisseria meningitidis, could provide cross-protection against N. gonorrhoeae.

Methods
The MenGO (Meningococcal vaccine efficacy against Gonorrhoea) study is a phase III open-label randomised control trial in GBM to evaluate the efficacy of the four-component meningococcal serogroup B vaccine, 4CMenB, against gonorrhoea. A total of 130 GBM will be recruited at the Gold Coast Sexual Health Clinic, Australia, and randomised to either receive 2 doses of 4CMenB or no intervention. Participants will be followed up for 24 months with testing for N. gonorrhoeae and other sexually transmissible infections every three months. Demographics, sexual behaviour risk, antibiotic use, and blood samples for analysis of N. gonorrhoeae-specific immune responses, will be collected during the study. The primary outcome is the number of N. gonorrhoeae infections in participants over 2 years measured by nucleic acid amplification test (NAAT). Secondary outcomes are vaccine-induced N. gonorrhoeae-specific immune responses, and adverse events in trial participants.

Discussion
This trial will determine if the 4CMenB vaccine is able to reduce N. gonorrhoeae infection. If shown to be effective, 4CMenB could be used in gonococcal prevention. Analysis of 4CMenB-induced immune responses will increase understanding of the type of immune response needed to prevent N. gonorrhoeae, which may enable identification of a potential correlate of protection to aid future gonorrhoea vaccine development.

Trial registration
The trial has been registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001478101) on 25 October 2019.
LncRNA LINC00205 stimulates osteoporosis and contributes to spinal fracture through the regulation of the miR-26b-5p/KMT2C axis
Authors: Wang Hongtao , Xu Weilin , Chen Xiaoqing , Mei Xiongfeng , Guo Zhonghua , Zhang Juan 
Published: April 2023

Abstract
Background
Osteoporosis (OP) is a common bone disease marked by decreased bone strength. Increasing evidence suggests that long non-coding RNA (lncRNAs) play important roles in the occurrence and progression of OP. This study aimed to investigate the role and mechanism of LINC00205 in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and OP.

Methods
Bone tissue samples were obtained from healthy controls and patients with osteoporosis with a spinal fracture (OP-Frx) or without a spinal fracture (OP-no-Frx). HMSCs were cultured and induced to undergo osteogenic differentiation. The expression of LINC00205, lysine (K)-specific methyltransferase 2C (KMT2C), and miR-26b-5p in bone tissues and cells was evaluated using western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of LINC00205, miR-26b-5p, and KMT2C on calcium deposition, alkaline phosphatase (ALP) activity, and mRNA levels of the osteogenic differentiation marker genes [ALP, osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2)] were investigated using alizarin red S staining, an ALP activity assay, and qRT-PCR, respectively. Dual-luciferase reporter assay was performed to ascertain the binding relationship between miR-26b-5p and LINC00205/KMT2C.

Results
LINC00205 and KMT2C were upregulated in patients with OP-Frx and OP-no-Frx, whereas miR-26b-5p was downregulated. Furthermore, LINC00205 and KMT2C expression decreased, whereas that of miR-26b-5p increased over time from day 7 to 21 of the osteogenic differentiation of hMSCs. The knockdown of LINC00205 and KMT2C significantly increased ALP activity, calcium deposition, and the expression of RUNX2, ALP, and OCN. In contrast, the inhibition of miR-26b-5p yielded the opposite result. These data suggest that LINC00205 inhibits the osteogenic differentiation of hMSCs by modulating the miR-26b-5p/KMT2C signaling axis.

Conclusion
LINC00205 promotes OP and is involved in spinal fractures. LINC00205 is also a potential negative regulator of the osteogenic differentiation of hMSCs.
Impact of digital health interventions for adolescents with type 1 diabetes mellitus on health literacy: a systematic review
Authors: Naef Aurélia Naoko , Wilhelm Christoph , Tezcan-Güntekin Hürrem , Amelung Volker Eric 
Published: April 2023

Abstract
Background
Evidence shows that living with diabetes mellitus type 1 (T1DM) in adolescent age is particularly challenging and difficult to manage. A high level of health literacy is important to prevent and avoid debilitating complications. Despite the increasing prevalence and incidence of T1DM by adolescent and the large use of digital health interventions, little is known about the association between this use and health literacy. This systematic review provides an overview on the impact of digital health interventions for adolescents with type 1 diabetes on health literacy and derive recommendations for further research.

Methods
Electronic searches were performed in five databases in Medline (Medline, PubMed + via PubMed), The Cochrane Library, EMBASE (via Ovid), Web of Science and PsycINFO from 2011 to 2021. In addition, grey literature searches were conducted in Google Scholar, OAlster and Trip. Relevant studies that have been missed by electronic and hand-searching strategies were searched in the reference lists of all included studies. The review followed PRISMA guidelines. Two researchers independently screened abstracts for initial eligibility and applied the inclusion and exclusion criteria to the relevant full-text articles. Quality was assessed using the tools RoB2 Cochrane, ROBINS I, NOS (Newcastle–Ottawa Scale), CASP (Critical Appraisal Skills Programme) for primary studies and Amstar-2 for secondary studies.

Results
Out of 981 studies, 22 were included in the final review. Most primary studies included in this review were judged as moderate overall risk of bias or with some concerns and most of the secondary studies as critically low quality reviews. Our findings suggest that the interplay of health care providers (HCP) and patients through social media helps the management of the disease. This corroborates Bröder et al.’ (2017) dimension of ‘communication and interactions’ in their concept of health literacy.

Conclusions
For adolescents with T1DM, social media may be a specific and beneficial intervention for an improved communication and interaction with their HCP. Further research should investigate what specific form of social media suits best for which adolescents.

Trial registration
The study protocol was registered on the 15th of November 2021 on Prospero (reg. NR: CRD42021282199).