bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia
Authors: Luskin Marlise R. , Shimony Shai , Keating Julia , Winer Eric S. , Garcia Jacqueline S. , Stone Richard M. , Jabbour Elias , Flamand Yael , Stevenson Kristen , Ryan Jeremy , Zeng Zhihong , Letai Anthony , Konopleva Marina , Jain Nitin , DeAngelo Daniel J. 
Published: November 2024

Abstract
In acute lymphoblastic leukemia (ALL), the B-cell lymphoma 2 inhibitor venetoclax may enhance the efficacy of chemotherapy, allowing dose reductions. This phase 1b study of venetoclax plus attenuated chemotherapy enrolled 19 patients with ALL either newly diagnosed (aged ≥60 years, n = 11 [B-cell, n = 8; T-cell, n = 3]) or relapsed/refractory (R/R; aged ≥18 years, n = 8 [B-cell, n = 3; T-cell, n = 5]). Venetoclax was given for 21 days with each cycle of mini–hyper-CVD (mini-HCVD; cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose-limiting toxicities at dose level 1 (DL1; n = 3, 400 mg/d) or DL2 (n = 6, 600 mg/d); DL2 was the recommended phase 2 dose and explored further (n = 10). The most common nonhematologic adverse events were grade ≥3 infections. There were no deaths within 60 days. There was no tumor lysis syndrome, hepatotoxicity, prolonged cytopenias, or early discontinuation for toxicity. Among patients with newly diagnosed ALL, 10 of 11 (90.9%) achieved a measurable residual disease–negative (&lt;0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53-mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n = 9) or completed protocol (n = 1). With a median follow-up of 60 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% confidence interval [CI], 35.5 to not available), with a 2-year DFS rate of 90% (95% CI, 71-100). Among patients with R/R ALL, 3 of 8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well tolerated with promising efficacy. This trial was registered at www.clinicaltrials.gov as #NCT03319901.
Predicting neurodevelopmental disorders using machine learning models and electronic health records – status of the field
Authors: Rajagopalan Shyam Sundar , Tammimies Kristiina 
Published: November 2024

AbstractMachine learning (ML) is increasingly used to identify patterns that could predict neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). One key source of multilevel data for ML prediction models includes population-based registers and electronic health records. These can contain rich information on individual and familial medical histories and socio-demographics. This review summarizes studies published between 2010–2022 that used ML algorithms to develop predictive models for NDDs using population-based registers and electronic health records. A literature search identified 1191 articles, of which 32 were retained. Of these, 47% developed ASD prediction models and 25% ADHD models. Classical ML methods were used in 82% of studies and in particular tree-based prediction models performed well. The sensitivity of the models was lower than 75% for most studies, while the area under the curve (AUC) was greater than 75%. The most important predictors were patient and familial medical history and sociodemographic factors. Using private in-house datasets makes comparing and validating model generalizability across studies difficult. The ML model development and reporting guidelines were adopted only in a few recently reported studies. More work is needed to harness the power of data for detecting NDDs early.
Whole-genome sequencing of copy number variation analysis in Ethiopian cattle reveals adaptations to diverse environments
Authors: Ayalew Wondossen , Xiaoyun Wu , Tarekegn Getinet Mekuriaw , Tessema Tesfaye Sisay , Chu Min , Liang Chunnian , Naboulsi Rakan , Van Damme Renaud , Bongcam-Rudloff Erik , Ping Yan 
Published: November 2024

Abstract
Background
Genomic structural variations (GSVs), notably copy number variations (CNVs), significantly shape genetic diversity and facilitate adaptation in cattle populations. Despite their importance, the genome-wide characterization of CNVs in indigenous Ethiopian cattle breeds—Abigar, Fellata, and Gojjam-Highland remains largely unexplored. In this study, we applied a read-depth approach to whole genome sequencing (WGS) data to conduct the first comprehensive analysis of CNVs in these populations.

Results
We identified 3,893 CNV regions (CNVRs) covering 19.15 Mb (0.71% of the cattle genome). These CNVRs ranged from 1.60 kb to 488.0 kb, with an average size of 4.92 kb. These CNVRs included deletions (1713), duplications (1929), and mixed events (251) showing notable differences in distribution among the breeds. Four out of five randomly selected CNVRs were successfully validated using real time polymerase chain reaction (qPCR). Further analyses identified candidate genes associated with high-altitude adaptation (GBE1 and SOD1), heat stress adaptation (HSPA13, DNAJC18, and DNAJC8) and resistance to tick infestations (BoLA and KRT33A). In addition, variance stabilizing transformation (VST) statistics highlighted population-specific CNVRs, emphasizing the unique genetic signatures of high-altitude adaptation in the Gojjam-Highland cattle breed. Among the detected CNVRs, 4.93% (192 out of 3,893) overlapped with 520 quantitative traits loci (QTLs) associated with six economically important trait categories suggesting that these CNVRs may significantly contribute to the genetic variation underlying these traits.

Conclusions
Our comprehensive analysis reveals significant CNVRs associated with key adaptive traits in Ethiopian cattle breeds highlighting their genetic diversity and resilience. These findings offer valuable insights into the genetic basis of adaptability and can inform sustainable breeding practices and conservation efforts. Future research should prioritize the functional validation of these CNVRs and their integration into breeding programs to enhance traits such as disease resistance and environmental adaptability.
Distalization of mandibular molar with iatrogenic root fracture in Class III malocclusion: a case report
Authors: Kim Hyojin , Hong Hyeon Gi , Jeon Ji Yoon , Lee Kee-Joon 
Published: November 2024

Abstract
Background
Placement of interradicular orthodontic miniscrews poses a potential risk of root damage, including superficial root contact and root fracture. This case report describes the iatrogenic root-injured tooth movement of a 27-year-old male with skeletal Class III malocclusion as nonsurgical orthodontic treatment.

Case presentation
An orthodontic miniscrew between the mandibular right first and second molars perforated the distal root of the mandibular first molar. A root fracture was discovered 4 months after miniscrew placement. Owing to the potential risk of ankylosis related to surgical intervention, a direct orthodontic distalizing force was applied towards the fractured distal root segment without additional treatment, resulting in considerable movement of the fractured tooth with maintaining tooth vitality. However, gradual root resorption of a fractured tooth with a separate root segment was observed. The mandibular arch distalization of skeletal Class III malocclusion was successfully performed and retained for 3 years 8 months with stable occlusion.

Conclusions
This case reveals a clinical remedy when root movement of a tooth with root fracture is indicated. The use of extra-alveolar miniscrews or miniplates can be considered for mandibular arch distalization to prevent potential root injuries caused by miniscrew placement.

Clinical trial number
Not applicable.
“I think all of us should have […] much better training in ethics.” Ethical challenges in policy making during the COVID-19 pandemic: Results from an interview study with Swiss policy makers and scientists
Authors: Brall Caroline , Gille Felix , Schlaufer Caroline , Porz Rouven , Jox Ralf J. 
Published: November 2024

Abstract
Background
The COVID-19 pandemic posed many unprecedented challenges to health care systems and public health efforts worldwide. Policy making and science were deeply intertwined, in particular with regard to the justification of health policy measures. In this context, ethical considerations were often at the core of decision-making trade-offs. However, not much is known about the actual ethical challenges encountered by policy makers and scientists involved in policy advice. With this study, we therefore aim to explore the ethical challenges during COVID-19-related political decision-making in Switzerland as perceived by policy makers and scientists involved in policy making. We also explore the role ethics advice had during the pandemic response and what can be learned for future public health crises.

Methods
We conducted thirteen qualitative expert interviews with policy makers and scientists involved in decision-making on COVID-19 policy responses in Switzerland on the regional and national level. We used inductive content analysis to analyse the interviews.

Results
Among the multitude of ethical challenges highlighted, interviewees perceived making trade-offs between the common good vs. the individual good and between economic welfare vs. health of the population, as well as proportionality of the policy measures, and the capacity of the public to accept uncertainty as central. Interviewees had diverging opinions on whether ethical considerations were sufficiently raised and discussed on the Swiss policy level during the COVID-19 pandemic. Among the reasons why ethics was not sufficiently discussed, they mentioned a lack of time in the fast-paced dynamic of the pandemic, ethics as a complex subject area, the interconnectedness between ethics and law, too much focus on few topics (mostly on vaccination-related ethical questions), and power relationships, such as dominance of medical professionals over ethicists. They evaluated ethics support to have been adequately present in the decision-making process, but wished for ethics training, involvement of the public in the discourse and for accompanying communication to build trust among the population for the future.

Conclusions
The study provides empirical insights into the ethical considerations of COVID-19 policy making in practice in Switzerland. It can help to develop ethics assistance for future crises and inform ethical health policy and decision-making not only in Switzerland, but also in other countries.
Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals
Authors: El-Shenawy Reem , Moustafa Rehab I. , Helmy Naiera M. , El-Abd Yasmine S. , Tabll Ashraf A. , Elesnawy Yasser K. , Shawky Heba 
Published: November 2024

Abstract
Background
Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis.

Methods
The study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR).

Results
Serum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients of chronic HCV, whereas their levels were significantly different between cirrhotic and non-cirrhotic SVRs (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185–<0.0001 and 0.0089–<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88–99.41% and 82.14–97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92–98%, respectively.

Conclusion
Serum sCD163, IL-10, IL-12 and peripheral Cldn1 and TGF-β expression levels represent novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.
Implementing a colostrum-kit reduces the time to first colostrum for neonates admitted to the NICU – a retrospective observational study
Authors: Hellström Sara , Linden Karolina , Sengpiel Verena , Elfvin Anders 
Published: November 2024

Abstract
Background
The World Health Organisation states that newborns should receive colostrum as soon as possible after birth. However, among newborns needing neonatal intensive care, initiation of lactation and access to colostrum might be delayed. At the centre of this study, a tertiary care hospital in Sweden (10,000 deliveries/year), few admitted infants received colostrum within the day of birth, warranting a quality improvement. In order to reduce the time from birth to first colostrum received by infants admitted to the Neonatal Intensive Care Unit (NICU), a new clinical routine including a colostrum-kit, was implemented as standard care in June 2018. The colostrum-kit contained information about hand expression of breastmilk as well as material for collecting, labelling and transporting the colostrum. The kit should be handed to all birthing parents with infants admitted to the NICU.

Methods
Data on time in minutes from birth to first colostrum administered to the infant (oral mouth care, oral feeding or gavage feeding) was retrieved for all infants born between 1 September 2016 and 31 October 2023, admitted to the NICU within 1h from birth. Infants were divided into four time-cohorts, compared with nonparametric ANOVA.

Results
The study included 3618 infants born at 22 + 0 – 43 + 0 weeks gestational age, of whom 2814 (78%) had available data on time to colostrum. Median (IQR) time in hours was 35 (20–36) pre-implementations, followed by 18 (7–38), 11 (4–26) and 8 (3–22) in the subsequent follow-up cohorts, p < 0.001. Subgroups of mode of delivery had median (IQR) pre-implementation of 30 (19–54) for vaginal and 47 (23–72) for caesarean section that reached 7 (2–18) and 9 (3–26) in the last follow-up. Subgroups of gestational age (< 28, 28–31, 32–36, > 36 weeks) had a pre-implementation time of 48 (26–80), 46 (23–73), 33 (20–60) and 32 (19–57), that in the last follow-up was reduced to 4 (2–20), 7 (2–29), 9 (2–33) and 9 (4–19).

Conclusions
Implementing a colostrum-kit for infants admitted to the NICU significantly reduced the time to first colostrum administered to the infant in all gestational ages. The difference between subgroups of gestational age or mode of delivery was reduced. The effect persisted over time.
Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis
Authors: Urrutia Samuel , Kantarjian Hagop M. , Ravandi-Kashani Farhad , Bueso-Ramos Carlos , Kanagal-Shamanna Rashmi , Jabbour Elias , Montalban-Bravo Guillermo , Short Nicholas J. , Daver Naval , Borthakur Gautam , Dinardo Courtney D. , Kadia Tapan M. , Masarova Lucia , Bose Prithviraj , Pemmaraju Naveen , Garcia-Manero Guillermo , Sasaki Koji 
Published: November 2024

AbstractThe outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0–1 and 148 (30.1%) had MF grade 2–3. Patients with MF 2–3 had a higher proportion of complex cytogenetics (39.2% vs. 24.7%, p = 0.002) JAK2 mutations (25.7% vs. 18%, p = 0.07) and lower proportion of IDH2 (16.9% vs. 25.9%, p = 0.03) and CEBPA (15.5% vs. 27.6%, p = 0.006) mutations. 64% were treated with low-intensity chemotherapy (LIT) and 36.1% with intensive chemotherapy (IT). The complete remission (CR)/CR with incomplete count recovery (CRi) rates were 63.5% with IC versus 37.9% with LIT (p = 0.007). In patients aged 60 or older 4-week mortality was 12.5% with IC vs. 9.3% with LIT (p = 0.8). The median overall survival (OS) was 14.2 with MF 0–1 versus 7.5 months with MF 2–3 (p < 0.005). In patients aged 60 or older with MF 2–3 median OS was 6.5 months with IT versus 7.0 months with LIT (p = 0.19). In a multivariate analysis, grade 2–3 MF (HR 2.0, 95%CI 1.59–2.51) was the strongest prognostic factor for survival. In summary, grade 2–3 MF in AML is associated with worse outcomes.
How should trial teams make decisions about the proportions and diversity of the ethnic groups in their trial?
Authors: Treweek Shaun , Gillies Katie , Witham Miles D. , Devane Declan , Khunti Kamlesh , Bower Peter , Parker Adwoa , Soulsby Irene , Ostrovska Bārbala , Prowse Sarah , Green Heidi 
Published: November 2024

Abstract
Background
The benefits of randomised trials are not shared equally, and people from ethnic minority groups are a key constituency under-served by clinical research and clinical care. The STRIDE project aimed to give trialists practical information about how to decide which ethnic groups should be in their trials, and at what proportion.

Methods
We considered trials in six clinical areas: cancer, cardiovascular, diabetes, maternal health, mental health, and smoking cessation. We created a summary for each, including participants–intervention–comparators–outcomes, and data on disease prevalence by ethnicity. These were discussed with panels with clinical expertise, trial and methodology expertise, lived experience, funding, and experience of working with and on behalf of ethnic communities. For each trial, we asked panel members to decide which ethnic groups should have been involved and at what proportion.

Results
We discussed 23 trials with 40 individual panel members. Panels found our questions difficult to answer. The lack of publicly available data on prevalence by ethnicity was central to this. Where data were available, decision-making was easier but not simple.
The discussions led to eight STRIDE recommendations. We recommend that discussions involve diverse teams and that discussions need time, with access to the best available data. In the absence of data or consensus, we recommend the adoption of ‘default’ minimum rates of inclusion, with oversampling considered. These discussions should inform site selection, and the practical challenges of recruitment and retention should not determine which groups are to be included.
We also suggest five policy initiatives to support implementation of the recommendations. Broadly, these are (1) funders need to signal that ethnic diversity is expected, (2) trial teams need access to better data, (3) funders and others need to signal that ethnic diversity means better science, (4) more funding is needed for evaluation, and (5) Good Clinical Practice training should cover ethnic diversity.

Conclusions
Agreeing targets for which ethnic groups to involve in a trial is essential but difficult. Our eight recommendations could help to make trials more ethnically diverse if followed, and we suggest five policy initiatives that would create a supportive environment for their implementation.
Genomic characterisation of an extended-spectrum β-Lactamase-producing Klebsiella pneumoniae isolate assigned to a novel sequence type (6914)
Authors: Akinyemi Muiz O. , Oyedele Oluwawapelumi A. , Kleyn Mariska S. , Onarinde Bukola A. , Adeleke Rasheed A. , Ezekiel Chibundu N. 
Published: November 2024

Abstract
Background
Cow milk, which is sometimes consumed raw, hosts a plethora of microorganisms, some of which are beneficial, while others raise food safety concerns. In this study, the draft genome of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae subsp. pneumoniae strain Cow102, isolated from raw cow milk used to produce traditional foods in Nigeria, is reported.

Result
The genome has a total length of 5,359,907 bp, with 70 contigs and a GC content of 57.35%. A total of 5,244 protein coding sequences were detected with 31% mapped to a subsystem, and genes coding for amino acids and derivatives being the most prevalent. Multilocus sequence typing revealed that the strain had new allelic profile assigned to the novel 6914 sequence type possessing capsular and lipopolysaccharide antigen K locus 122 with an unknown K type (KL122) and O locus O1/O2v2 with type O2afg, respectively. A total of 28 resistance-related genes, 98 virulence-related genes, two plasmids and five phages were identified in the genome. The resistance genes oqxA, oqxB and an IS3 belonging to cluster 204 were traced to bacteriophage Escher 500,465. Comparative analysis predicted one strain specific orthologous group comprising three genes.

Conclusion
This report of a novel sequence type (ST6914) in K. pneumoniae presents a new allelic profile, indicating ongoing evolution and diversification within the species. Its uniqueness suggests it may represent a locally evolved lineage, although further sampling would be necessary to confirm this hypothesis. The strain’s multidrug resistance, virulence gene repertoire, and isolation from animal milk render it a potentially significant public health concern, underscoring the importance of genomic surveillance in non-clinical settings to detect emerging strains. Further research is required to fully characterise the capsular K type of ST6914.