bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer
Authors: Kendzia Sandra , Franke Susanne , Kröhler Tarek , Golob-Schwarzl Nicole , Schweiger Caroline , Toeglhofer Anna M. , Skofler Christina , Uranitsch Stefan , El-Heliebi Amin , Fuchs Julia , Punschart Andreas , Stiegler Philipp , Keil Marlen , Hoffmann Jens , Henderson David , Lehrach Hans , Yaspo Marie-Laure , Reinhard Christoph , Schäfer Reinhold , Keilholz Ulrich , Regenbrecht Christian , Schicho Rudolf , Fickert Peter , Lax Sigurd F. , Erdmann Frank , Schulz Marcel H. , Kiemer Alexandra K. , Haybaeck Johannes , Kessler Sonja M. 
Published: May 2023

Abstract
Aim
Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches.

Methods
Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses.

Results
We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells.

Conclusions
IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.
Conservative management following patellar dislocation: a level I systematic review
Authors: Flores Gustavo Wickert , de Oliveira Deise Ferreira , Ramos Ana Paula Silveira , Sanada Luciana Sayuri , Migliorini Filippo , Maffulli Nicola , Okubo Rodrigo 
Published: May 2023

Abstract
Background
Patellar instability is a common and disabling clinical condition. Treatment of acute primary patellar dislocation aims to reduce the risk of recurrence or painful subluxation and improve function. However, the actual clinical efficacy of any management modality following an acute dislocation has never been demonstrated in prospective or retrospective studies, and the optimal way in which the various management modalities should be used is at best unclear.

Methods
A search was conducted in PubMed, Bireme and Embase databases. Inclusion criteria followed the acronym PICOS, (P) subjects with patellar instability, (I) therapeutic interventions, (C) placebo or control or surgical treatments, (O) rate of dislocations and function, and (S) clinical trials. The Medical Subject Headings (MeSH) terms used were: ((“patellar instability”) OR (“patellar dislocation”)) AND ((physiotherapy) OR (rehabilitation) OR (“conservative treatment”) OR (therapy) OR (therapeutic)). The risk of bias was analysed using the PeDRO scale.

Results
Seven randomized controlled trials including 282 patients were considered. The quality of studies detailing the results of conservative treatment was higher than that of surgical procedures, but all studies have relatively low methodological quality. Four studies compared physiotherapeutic interventions with surgical procedures, and three studies compared conservative intervention techniques.

Conclusion
An unstructured lower limb physical therapy programme evidences similar outcomes to specific exercises. Surgical management is associated with a lower rate of re-dislocation; however, whether surgery produces greater functional outcomes than conservative management is still unclear. The use of a knee brace with a limited range of motion, stretching and neuromuscular exercises are the most commonly recommended physiotherapy methodologies.
Progesterone from ovulatory menstrual cycles is an important cause of breast cancer
Authors: Coelingh Bennink Herjan J. T. , Schultz Iman J. , Schmidt Marcus , Jordan V. Craig , Briggs Paula , Egberts Jan F. M. , Gemzell-Danielsson Kristina , Kiesel Ludwig , Kluivers Kirsten , Krijgh Jan , Simoncini Tommaso , Stanczyk Frank Z. , Langer Robert D. 
Published: May 2023

AbstractMany factors, including reproductive hormones, have been linked to a woman’s risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman’s lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.
Breast metastatic tumors in lung can be substituted by lung-derived malignant cells transformed by alternative splicing H19 lncRNA
Authors: Xu Jin Biao , Cao Jun , Xia Jin , Zhu Ying , He Yi , Cao Ming Guo , Fang Bing Mu , Thiery Jean Paul , Zhou Wu 
Published: May 2023

AbstractMetastasis accounts for most cancer-associated deaths; yet, this complex process remains poorly understood, particularly the relationship between distant metastasis and primary site-derived cells. Here, we modified the classical MMTV–PyMT breast carcinoma model to trace the fate of mammary-derived carcinoma cells. We show that within the lung, when the metastatic breast carcinoma cells are conditionally depleted, transformed lung epithelial cells generate new metastases. Metastatic breast carcinoma cells transmit H19 long noncoding (lnc) RNA to lung epithelial cells through exosomes. SF3B1 bearing mutations at arginine-625 alternatively splices H19 lncRNA in lung epithelial cells, which selectively acts like a molecular sponge to sequester let-7a and induces Myc upregulation. Under the conditional elimination of primary site-derived breast carcinoma cells, lung malignant cells expressing the mutated SF3B1 splice variant dominate the newly created tumors. Our study suggests that these new carcinoma cells originating from within the colonized organ can replace the primary site-derived malignant cells whenever their expansion is abrogated using an inducible diphtheria toxin receptor in our designed system. These findings should call for a better understanding of metastatic tumors with the specific origin during cancer metastasis.
ZNF330/NOA36 interacts with HSPA1 and HSPA8 and modulates cell cycle and proliferation in response to heat shock in HEK293 cells
Authors: Sanchez-Briñas Alejandra , Duran-Ruiz Carmen , Astola Antonio , Arroyo Marta Marina , Raposo Fátima G. , Valle Antonio , Bolivar Jorge 
Published: May 2023

Abstract
Background
The human genome contains nearly 20.000 protein-coding genes, but there are still more than 6,000 proteins poorly characterized. Among them, ZNF330/NOA36 stand out because it is a highly evolutionarily conserved nucleolar zinc-finger protein found in the genome of ancient animal phyla like sponges or cnidarians, up to humans. Firstly described as a human autoantigen, NOA36 is expressed in all tissues and human cell lines, and it has been related to apoptosis in human cells as well as in muscle morphogenesis and hematopoiesis in Drosophila. Nevertheless, further research is required to better understand the roles of this highly conserved protein.

Results
Here, we have investigated possible interactors of human ZNF330/NOA36 through affinity-purification mass spectrometry (AP-MS). Among them, NOA36 interaction with HSPA1 and HSPA8 heat shock proteins was disclosed and further validated by co-immunoprecipitation. Also, “Enhancer of Rudimentary Homolog” (ERH), a protein involved in cell cycle regulation, was detected in the AP-MS approach. Furthermore, we developed a NOA36 knockout cell line using CRISPR/Cas9n in HEK293, and we found that the cell cycle profile was modified, and proliferation decreased after heat shock in the knocked-out cells. These differences were not due to a different expression of the HSPs genes detected in the AP-MS after inducing stress.

Conclusions
Our results indicate that NOA36 is necessary for proliferation recovery in response to thermal stress to achieve a regular cell cycle profile, likely by interaction with HSPA1 and HSPA8. Further studies would be required to disclose the relevance of NOA36-EHR interaction in this context.
Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study
Authors: Schoenbuchner Simon M. , Huang Chao , Waldron Cherry-Ann , Thomas-Jones Emma , Hood Kerenza , Carrol Enitan D. , Pallmann Philip 
Published: May 2023

Abstract
Introduction
The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study.

Methods
The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up.

Results
Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age.

Conclusion
We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up.

Trial registration
BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832.
PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.
Association of triglyceride-glucose index with early neurological deterioration events in patients with acute ischemic stroke
Authors: Wang Jia , Tang Hao , Wang Xiaokun , Wu Jiarong , Gao Jiaqi , Diao Shuang , Wu Yun 
Published: May 2023

Abstract
Background
The Triglyceride and Glucose (TyG) index has been found to have a strong correlation with the recurrence of acute ischemic stroke (AIS) and poor patient outcomes. Nevertheless, the relationship between the TyG index and early neurological deterioration (END) has not been fully explored. Therefore, the present study aims to investigate the potential association between the TyG index and END.

Methods
A retrospective analysis of 2129 patients diagnosed with AIS between January 2019 and December 2022 at the Second Affiliated Hospital of Harbin Medical University. Patients were divided into END and non-END groups based on changes in National Institutes of Health Stroke Scale scores within 7 days of admission, and the differences in the indicators between the two groups were examined using univariate analysis. The patients were then divided into three groups based on the tertile of the TyG index (T1: TyG index < 8.662; T2: 8.662 ≤ TyG index < 9.401; T3: TyG index ≥ 9.401), and logistic regression analysis was used to examine the association between the TyG index and END. Finally, the predictive ability of the TyG index was evaluated using the receiver operating characteristic (ROC) curve.

Results
A total of 724 patients experienced END. The results of the analysis showed that the TyG index was significantly higher in the END group compared to the non-END group. Furthermore, the TyG index was found to be an independent risk factor for the development of END (OR, 1.561; 95% 1.166–2.090, P = 0.003). After adjusting for confounders, the risk of END was 3.953 (95% CI 2.793–5.595; P < 0.001) and 5.906 (95% CI 3.676–9.488; P < 0.001) times higher in the T2 and T3 groups, respectively, in contrast to the T1 group. The area under the ROC curve of the TyG index was 0.711 (0.688–0.733), indicating an excellent predictive indicator.

Conclusions
Our study uncovered that higher TyG index levels were associated with END development in AIS patients.
The gut microbiome modifies the associations of short- and long-term physical activity with body weight changes
Authors: Wang Kai , Mehta Raaj S. , Ma Wenjie , Nguyen Long H. , Wang Dong D. , Ghazi Andrew R. , Yan Yan , Al-Shaar Laila , Wang Yiqing , Hang Dong , Fu Benjamin C. , Ogino Shuji , Rimm Eric B. , Hu Frank B. , Carmody Rachel N. , Garrett Wendy S. , Sun Qi , Chan Andrew T. , Huttenhower Curtis , Song Mingyang 
Published: May 2023

Abstract
Background
The gut microbiome regulates host energy balance and adiposity-related metabolic consequences, but it remains unknown how the gut microbiome modulates body weight response to physical activity (PA).

Methods
Nested in the Health Professionals Follow-up Study, a subcohort of 307 healthy men (mean[SD] age, 70[4] years) provided stool and blood samples in 2012–2013. Data from cohort long-term follow-ups and from the accelerometer, doubly labeled water, and plasma biomarker measurements during the time of stool collection were used to assess long-term and short-term associations of PA with adiposity. The gut microbiome was profiled by shotgun metagenomics and metatranscriptomics. A subcohort of 209 healthy women from the Nurses’ Health Study II was used for validation.

Results
The microbial species Alistipes putredinis was found to modify the association between PA and body weight. Specifically, in individuals with higher abundance of A. putredinis, each 15-MET-hour/week increment in long-term PA was associated with 2.26 kg (95% CI, 1.53–2.98 kg) less weight gain from age 21 to the time of stool collection, whereas those with lower abundance of A. putredinis only had 1.01 kg (95% CI, 0.41–1.61 kg) less weight gain (pinteraction = 0.019). Consistent modification associated with A. putredinis was observed for short-term PA in relation to BMI, fat mass%, plasma HbA1c, and 6-month weight change. This modification effect might be partly attributable to four metabolic pathways encoded by A. putredinis, including folate transformation, fatty acid β-oxidation, gluconeogenesis, and stearate biosynthesis.

Conclusions
A greater abundance of A. putredinis may strengthen the beneficial association of PA with body weight change, suggesting the potential of gut microbial intervention to improve the efficacy of PA in body weight management.
Factor structure and psychometric properties of the german version chronic uncertainty scale (CU-20)
Authors: Schmalbach Ileana , Bastianon Christina Diane , Afifi Walid A. , Franke Gabriele Helga , Hinz Andreas , Petrowski Katja 
Published: May 2023

Abstract
Background
The experience of uncertainty is ubiquitous and universal across the globe. Many available tools measuring uncertainty are focused on one aspect of uncertainty, e.g., patients with life-threatening illnesses, hence a measure considering (chronic) uncertainty as an integral experience reflect ongoing uncertainties from a socio-cultural perspective is missing. Additionally, current tools do not account for an extended timeframe to measure chronic forms of uncertainty. The objective of this study is to validate a translated German version of the 20 item Chronic Uncertainty Scale (CU-20).

Methods
The full sample comprised N = 462 participants. Most of the participants were young German citizens and the sex distribution was relatively balanced (60% females; age in average: M = 24.56; SD = 4.78). Using equally split samples, an exploratory factor analysis (EFA) evaluated the CU-20 factor structure, followed by a confirmatory factor analysis (CFA) to test the established factor structure. Measurement invariance between male and female groups was evaluated. Internal consistency of the six-factor model was shown and scale discrimination was shown against chronic stress.

Results
The EFA results showed decent model fit for the five-factor structure, however based on the CFA results, the theoretically established six-factor model fits the data significantly better. Measurement invariance between male and female groups was shown to be clearly scalar invariant. Cronbach’s alpha, omega and lambda all support internal consistency and reliability of CU-20.

Conclusions
The CU-20 is a valid and reliable measure of one’s state of chronic uncertainty reflecting the individuals’ experiences of macrosocial forms of uncertainty, compared to the existing ones. This scale is especially useful in the context of migration, refugees or during global crises. Further psychometric testing is required in more diverse samples and a deeper look into measurement invariance is recommended.
Combining accelerometry with allometry for estimating daily energy expenditure in joules when in-lab calibration is unavailable
Authors: Chakravarty Pritish , Cozzi Gabriele , Scantlebury David Michael , Ozgul Arpat , Aminian Kamiar 
Published: May 2023

Abstract
Background
All behaviour requires energy, and measuring energy expenditure in standard units (joules) is key to linking behaviour to ecological processes. Animal-borne accelerometers are commonly used to infer proxies of energy expenditure, termed ‘dynamic body acceleration’ (DBA). However, converting acceleration proxies (m/s2) to standard units (watts) involves costly in-lab respirometry measurements, and there is a lack of viable substitutes for empirical calibration relationships when these are unavailable.

Methods
We used past allometric work quantifying energy expenditure during resting and locomotion as a function of body mass to calibrate DBA. We used the resulting ‘power calibration equation’ to estimate daily energy expenditure (DEE) using two models: (1) locomotion data-based linear calibration applied to the waking period, and Kleiber’s law applied to the sleeping period (ACTIWAKE), and (2) locomotion and resting data-based linear calibration applied to the 24-h period (ACTIREST24). Since both models require locomotion speed information, we developed an algorithm to estimate speed from accelerometer, gyroscope, and behavioural annotation data. We applied these methods to estimate DEE in free-ranging meerkats (Suricata suricatta), and compared model estimates with published DEE measurements made using doubly labelled water (DLW) on the same meerkat population.

Results
ACTIWAKE’s DEE estimates did not differ significantly from DLW (t(19) = − 1.25; P = 0.22), while ACTIREST24’s estimates did (t(19) = − 2.38; P = 0.028). Both models underestimated DEE compared to DLW: ACTIWAKE by 14% and ACTIREST by 26%. The inter-individual spread in model estimates of DEE (s.d. 1–2% of mean) was lower than that in DLW (s.d. 33% of mean).

Conclusions
We found that linear locomotion-based calibration applied to the waking period, and a ‘flat’ resting metabolic rate applied to the sleeping period can provide realistic joule estimates of DEE in terrestrial mammals. The underestimation and lower spread in model estimates compared to DLW likely arise because the accelerometer only captures movement-related energy expenditure, whereas DLW is an integrated measure. Our study offers new tools to incorporate body mass (through allometry), and changes in behavioural time budgets and intra-behaviour changes in intensity (through DBA) in acceleration-based field assessments of daily energy expenditure.