bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes
Authors: Olbertova Helena , Plevova Karla , Pavlova Sarka , Malcikova Jitka , Kotaskova Jana , Stranska Kamila , Spunarova Michaela , Trbusek Martin , Navrkalova Veronika , Dvorackova Barbara , Tom Nikola , Pal Karol , Jarosova Marie , Brychtova Yvona , Panovska Anna , Doubek Michael , Pospisilova Sarka 
Published: February 2022

Abstract
Background
Telomeres are protective structures at chromosome ends which shorten gradually with increasing age. In chronic lymphocytic leukemia (CLL), short telomeres have been associated with unfavorable disease outcome, but the link between clonal evolution and telomere shortening remains unresolved.

Methods
We investigated relative telomere length (RTL) in a well-characterized cohort of 198 CLL patients by qPCR and focused in detail on a subgroup 26 patients who underwent clonal evolution of TP53 mutations (evolTP53). In the evolTP53 subgroup we explored factors influencing clonal evolution and corresponding changes in telomere length through measurements of telomerase expression, lymphocyte doubling time, and BCR signaling activity.

Results
At baseline, RTL of the evolTP53 patients was scattered across the entire RTL spectrum observed in our CLL cohort. RTL changed in the follow-up samples of 16/26 (62%) evolTP53 cases, inclining to reach intermediate RTL values, i.e., longer telomeres shortened compared to baseline while shorter ones prolonged. For the first time we show that TP53 clonal shifts are linked to RTL change, including unexpected RTL prolongation. We further investigated parameters associated with RTL changes. Unstable telomeres were significantly more frequent among younger patients (P = 0.032). Shorter telomeres were associated with decreased activity of the B-cell receptor signaling components p-ERK1/2, p-ZAP-70/SYK, and p-NFκB (P = 0.04, P = 0.01, and P = 0.02, respectively).

Conclusions
Our study revealed that changes of telomere length reflect evolution in leukemic subclone proportion, and are associated with specific clinico-biological features of the explored cohort.
Healthcare professionals’ longitudinal perceptions of group phenomena as determinants of self-assessed learning in organizational communities of practice
Authors: Durand François , Richard Lucie , Beaudet Nicole , Fortin-Pellerin Laurence , Hudon Anahi Morales , Tremblay Marie-Claude 
Published: February 2022

AbstractBackgroundGiven the importance of continuous learning as a response to the increasing complexity of health care practice, there is a need to better understand what makes communities of practice in health effective at fostering learning. Despite the conceptual stance that communities of practice facilitate individual learning, the scientific literature does not offer much evidence for this. Known factors associated with the effectiveness of communities of practice – such as collaboration, psychological safety within the community, and commitment to the community – have been studied in cross-sectional qualitative designs. However, no studies to date have used a quantitative predictive design. The objective of this study is to assess how members of a community of practice perceive interactions among themselves and determine the extent to which these interactions predict self-assessed learning over time.MethodsData was collected using validated questionnaires from six communities of practice (N = 83) in four waves of measures over the course of 36 months and was analysed by means of General Estimating Equations. This allowed to build a longitudinal model of the associations between perceptions of collaboration, psychological safety within the community, commitment to the community and self-assessed learning over time.ResultsPerception of collaboration in the community of practice, a personal sense of psychological safety and a commitment to the community of practice are predictors longitudinally associated with self-assessed learning.ConclusionsIn terms of theory, conceptual links can be made between intensity of collaboration and learning over time in the context of a community of practice. Recent work on psychological safety suggests that it is still unclear whether psychological safety acts as a direct enhancer of learning or as a remover of barriers to learning. This study’s longitudinal results suggest that psychological safety may enhance how and to what extent professionals feel they learn over time. Commitment towards the community of practice is a strong predictor of learning over time, which hints at differential effects of affective, normative and continuance commitment. Communities of practice can therefore apply these findings by making collaboration, psychological safety, commitment and learning regular reflexive topics of discussion.
Clinical guidelines for managing hearing loss as a complication of drug-resistant tuberculosis treatment: an evaluation of implementation fidelity in Kano, Nigeria
Authors: Muhammad Sani Ibrahim , Eboreime Ejemai Amaize , Ogbonna Vivian Ifeoma , Zubairu Iliyasu , Ibisomi Latifat 
Published: February 2022

Abstract
Background
Nigeria has a high burden of Tuberculosis (TB) including Drug-resistant Tuberculosis (DR-TB) and hearing loss. Despite several efforts directed toward its control, many patients fail to respond to treatment, having developed DR-TB. Lack of adherence to the DR-TB guidelines/improper implementation of the guideline has been identified as one of the factors impeding on effective treatment. This study sought to measure the implementation fidelity of health workers to management guidelines for hearing loss resulting from DR-TB treatment and to identify its determinants.

Method
A questionnaire-based cross-sectional study was conducted at the Infectious Disease Hospital, Kano. Implementation fidelity of the Programmatic Management guidelines for the treatment of Drug-resistant Tuberculosis was measured under the four domains of content, coverage, duration and frequency. The determinants examined are intervention complexity, facilitation strategies, quality of delivery and participant responsiveness as proposed by the Carroll et al. framework. Other determinants used are age, sex, professional cadre and work experience of healthcare providers.

Results
The Implementation fidelity score ranged from 40 to 64% with a mean of 47.6%. Quality of delivery, intervention complexity, participants’ responsiveness, and being a medical doctor exerted a positive effect on implementation fidelity while facilitation strategy, age and work experience exerted a negative effect on implementation fidelity.

Conclusion
The implementation fidelity of management guidelines for hearing loss resulting from DR-TB treatment was low. Implementation fidelity should be assessed early and at intervals in the course of implementing the Programmatic Management of Drug-resistant Tuberculosis guideline and indeed, in the implementation of any intervention.
Xq26.3-q27.1 duplication including SOX3 gene in a Chinese boy with hypopituitarism: case report and two years treatment follow up
Authors: Du Caiqi , Wang Feiya , Li Zhuoguang , Zhang Mini , Yu Xiao , Liang Yan , Luo Xiaoping 
Published: February 2022

Abstract
Background
SOX3 is essential for pituitary development normally at the earliest stages of development. In humans, variants of SOX3 can cause X-linked hypopituitarism with various clinical manifestations, with or without mental retardation.

Case presentation
We present an 8-year-old Chinese patient with congenital hypopituitarism who had a 6.180 Mb duplication on Xq26.3q27.1 including SOX3, F9, and eight other contiguous genes. The main complains of the boy was short stature. His height was 90.1 cm (− 5.87SDS), weight 11.5 kg (− 5.25SDS). He developed growth hormone (GH) deficiency, cryptorchidism and low thyroid function. Pituitary magnetic resonance imaging revealed the pituitary dysplasia. After diagnosis, levothyroxine was given for one month first, and the thyroid function basically returned to normal, but the growth situation did not improve at all. Then recombinant human GH was given, his height, growth rate and height SDS were improved significantly in the 2 years follow-up. The level of height SDS improved from − 5.87 SDS before treatment to − 3.27 SDS after the first year of treatment and − 1.78 SDS after the second years of treatment. Gonadal function and long-term prognosis of the patient still need further observation and follow-up.

Conclusions
This is the first case of Chinese male patient with multiple hypophysis dysfunction caused by SOX3 duplication, which will expand the range of phenotypes observed in patients with duplication of SOX3.
Hypoxic stress disrupts HGF/Met signaling in human trophoblasts: implications for the pathogenesis of preeclampsia
Authors: Li Guanlin , Wang Yongqing , Cao Guangming , Ma Yeling , Li Yu-Xia , Zhao Yangyu , Shao Xuan , Wang Yan-Ling 
Published: February 2022

Abstract
Background
Preeclampsia (PE), a placenta-associated pregnancy complication, is the leading cause of maternal and perinatal morbidity and mortality. Met/Erk signaling is inhibited in the placentas of patients with early-onset preeclampsia (E-PE), but the underlying mechanisms remain elusive. In this study, the expression modes of Met and endocytic vesicles in normal and preeclamptic placentas were compared. Biotinylation internalization/recycling assays were used to measure the endocytosis of Met under hypoxia and normoxia in HTR8/SVneo cells. In addition, the expression level of Cbl, a specific E3 ligase of Met, was measured under hypoxia and normoxia, and the endocytosis of Met was studied by using confocal microscopy.

Results
We found considerable intracellular accumulation of Met, which was colocalized with caveolin-1 (CAV-1), in trophoblasts from E-PE placentas. Prolonged hypoxic stimulation led to the remarkable augmentation of CAV-1-mediated Met endocytosis in HTR8/SVneo cells. In addition, the expression of Cbl was substantially repressed by sustained hypoxia, disrupting ubiquitin degradation and the subsequent intracellular accumulation of Met in HTR8/SVneo cells. The abnormal degradation of Met hampered the ability of hepatocyte growth factor (HGF) to promote trophoblast cell invasion. In E-PE placentas, aberrant upregulation of CAV-1 and downregulation of Cbl were observed in parallel to the intracellular accumulation of Met.

Conclusions
These findings reveal that prolonged hypoxic stress induces the augmentation of endocytosis and repression of ubiquitin-mediated Met degradation, which leads to the impaired regulation of trophoblast invasion by HGF/Met signaling. These data provide novel evidence for elucidating the pathogenesis of preeclampsia, especially of the early-onset subtype.
Molecular evidence reveals thyrotropin intervention enhances the risk of developing radioiodine-refractory differentiated thyroid carcinoma
Authors: Samimi Hilda , Haghpanah Vahid 
Published: February 2022

AbstractRadioiodine (RAI) is the mainstay of treatment for differentiated thyroid carcinoma (DTC) following total thyroidectomy. Nevertheless, about 5% of patients with DTC are RAI-refractory (RAI-R). Understanding the molecular mechanisms associated with DTC during progression towards RAI-R DTC, including thyroid-stimulating hormone levels, may help to explain the pathophysiology of challenging RAI-R DTC clinical cases.
Graphical Abstract
Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification
Authors: Hu Yiyang , Gong Chunli , Li Zhibin , Liu Jiao , Chen Yang , Huang Yu , Luo Qiang , Wang Sumin , Hou Yu , Yang Shiming , Xiao Yufeng 
Published: February 2022

Abstract
Background
Gastric cancer (GC) is one of the most pernicious tumors that seriously harm human healthcare. GC metastasis is one of the prime cause of failed cancer treatment, but correlation between N6-methyladenosine (m6A) and GC metastasis was less reported.

Methods
Methylated RNA immunoprecipitation sequencing (MeRIP-seq) of GC tissues was conducted. Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) were taken to determine the expression of ALKBH5 in GC tissues and cell lines. RNA-seq together with MeRIP-qRT-PCR was used to screen the target gene of ALKBH5. RNA pulldown, mass spectrometry and RNA immunoprecipitation (RIP) were used to search the “reader” protein of target gene. The mechanism was also validated via a tail vein injection method for lung metastasis model.

Results
Decreased expression of ALKBH5 was detected in GC samples, and it was correlated with clinical tumor distal metastasis and lymph node metastasis. ALKBH5 interference promoted metastasis of GC cells and this effect was closely related to the demethylase activity of ALKBH5. PKMYT1, as a downstream target of ALKBH5, promoted invasion and migration in GC. Caused by ALKBH5 knockdown or its demethylase activity mutation, upregulated expression of PKMYT1 indicated that ALKBH5 modulates expression of PKMYT1 in an m6A-dependent manner. IGF2BP3 helped stabilize the mRNA stability of PKMYT1 via its m6A modification site.

Conclusions
This study established an ALKBH5-PKMYT1-IGF2BP3 regulation system in metastasis, representing a new therapeutic target for GC metastasis.
An invasive Haemophilus influenzae serotype b infection in an Anglo-Saxon plague victim
Authors: Guellil Meriam , Keller Marcel , Dittmar Jenna M. , Inskip Sarah A. , Cessford Craig , Solnik Anu , Kivisild Toomas , Metspalu Mait , Robb John E. , Scheib Christiana L. 
Published: February 2022

AbstractBackgroundThe human pathogenHaemophilus influenzaewas the main cause of bacterial meningitis in children and a major cause of worldwide infant mortality before the introduction of a vaccine in the 1980s. Although the occurrence of serotype b (Hib), the most virulent type ofH. influenzae, has since decreased, reports of infections with other serotypes and non-typeable strains are on the rise. While non-typeable strains have been studied in-depth, very little is known of the pathogen’s evolutionary history, and no genomes dating prior to 1940 were available.ResultsWe describe a Hib genome isolated from a 6-year-old Anglo-Saxon plague victim, from approximately 540 to 550 CE, Edix Hill, England, showing signs of invasive infection on its skeleton. We find that the genome clusters in phylogenetic division II with Hib strain NCTC8468, which also caused invasive disease. While the virulence profile of our genome was distinct, its genomic similarity to NCTC8468 points to mostly clonal evolution of the clade since the 6th century. We also reconstruct a partialYersinia pestisgenome, which is likely identical to a published first plague pandemic genome of Edix Hill.ConclusionsOur study presents the earliest genomic evidence forH. influenzae, points to the potential presence of larger genomic diversity in the phylogenetic division II serotype b clade in the past, and allows the first insights into the evolutionary history of this major human pathogen. The identification of both plague and Hib opens questions on the effect of plague in immunocompromised individuals already affected by infectious diseases.
Species-targeted sorting and cultivation of commensal bacteria from the gut microbiome using flow cytometry under anaerobic conditions
Authors: Bellais Samuel , Nehlich Mélanie , Ania Maryne , Duquenoy Aurore , Mazier Wilfrid , van den Engh Ger , Baijer Jan , Treichel Nicole Simone , Clavel Thomas , Belotserkovsky Ilia , Thomas Vincent 
Published: February 2022

AbstractBackgroundThere is a growing interest in using gut commensal bacteria as “next generation” probiotics. However, this approach is still hampered by the fact that there are few or no strains available for specific species that are difficult to cultivate. Our objective was to adapt flow cytometry and cell sorting to be able to detect, separate, isolate, and cultivate new strains of commensal species from fecal material. We focused on the extremely oxygen sensitive (EOS) speciesFaecalibacterium prausnitziiand the under-represented, health-associated keystone speciesChristensenella minutaas proof-of-concept.ResultsA BD Influx® cell sorter was equipped with a glovebox that covered the sorting area. This box was flushed with nitrogen to deplete oxygen in the enclosure. Anaerobic conditions were maintained during the whole process, resulting in only minor viability loss during sorting and culture of unstainedF. prausnitziistrains ATCC 27766, ATCC 27768, and DSM 17677. We then generated polyclonal antibodies against target species by immunizing rabbits with heat-inactivated bacteria. Two polyclonal antibodies were directed againstF. prausnitziitype strains that belong to different phylogroups, whereas one was directed againstC. minutastrain DSM 22607. The specificity of the antibodies was demonstrated by sorting and sequencing the stained bacterial fractions from fecal material. In addition, staining solutions including LIVE/DEAD™ BacLight™ Bacterial Viability staining and polyclonal antibodies did not severely impact bacterial viability while allowing discrimination between groups of strains. Finally, we combined these staining strategies as well as additional criteria based on bacterial shape forC. minutaand were able to detect, isolate, and cultivate newF. prausnitziiandC. minutastrains from healthy volunteer’s fecal samples.ConclusionsTargeted cell-sorting under anaerobic conditions is a promising tool for the study of fecal microbiota. It gives the opportunity to quickly analyze microbial populations, and can be used to sort EOS and/or under-represented strains of interest using specific antibodies, thus opening new avenues for culture experiments.
Dissecting the genetic architecture of suicide attempt and repeated attempts in Korean patients with bipolar disorder using polygenic risk scores
Authors: Lee Dongbin , Baek Ji Hyun , Ha Kyooseob , Cho Eun-Young , Choi Yujin , Yang So-Yung , Kim Ji Sun , Cho Yunji , Won Hong-Hee , Hong Kyung Sue 
Published: February 2022

Abstract
Background
Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD.

Methods
The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive–compulsive disorder (OCD).

Results
The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke’s R2 = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke’s R2 = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke’s R2 = 4.91%, OR = 1.53, p = 0.043).

Conclusion
The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders.
Modeling neighborhood-scale shallow geothermal energy utilization: a case study in Berlin
Authors: Randow Jakob , Chen Shuang , Lubashevsky Katrin , Thiel Steve , Reinhardt Tom , Rink Karsten , Grimm Rüdiger , Bucher Anke , Kolditz Olaf , Shao Haibing 
Published: February 2022

AbstractNowadays, utilizing shallow geothermal energy for heating and cooling buildings has received increased interest in the building sector. Among different technologies, large borehole heat exchanger arrays are widely employed to supply heat to various types of buildings. Recently, a 16-borehole array was constructed to extract shallow geothermal energy to provide heat to a newly-developed public building in Berlin. To guarantee the quality of the numerical model and reveal its sensitivity to different subsurface conditions, model simulations were conducted for 25 years with two finite element simulators, namely the open-source code OpenGeoSys and the widely applied commercial software FEFLOW. Given proper numerical settings, the simulation results from OpenGeoSys and FEFLOW are in good agreement. However, further analysis reveals differences with respect to borehole inflow temperature calculation implemented in the two software. It is found that FEFLOW intrinsically uses the outflow temperature from the previous time step to determine the current inflow temperature, which makes it capable of much faster simulation by avoiding iterations within a single time step. In comparison, OpenGeoSys always updates the inflow and outflow temperature based on their current time step values. Because the updates are performed after each iteration, it delivers more accurate results with the expense of longer simulation time. Based on this case study, OpenGeoSys is a valid alternative to FEFLOW for modeling ground source heat pump systems. For modellers working in this field, it is thus recommended to adopt small enough time step size, so that potential numerical error can be avoided.
Freely available convolutional neural network-based quantification of PET/CT lesions is associated with survival in patients with lung cancer
Authors: Borrelli Pablo , Góngora José Luis Loaiza , Kaboteh Reza , Ulén Johannes , Enqvist Olof , Trägårdh Elin , Edenbrandt Lars 
Published: February 2022

Abstract
Background
Metabolic positron emission tomography/computed tomography (PET/CT) parameters describing tumour activity contain valuable prognostic information, but to perform the measurements manually leads to both intra- and inter-reader variability and is too time-consuming in clinical practice. The use of modern artificial intelligence-based methods offers new possibilities for automated and objective image analysis of PET/CT data.

Purpose
We aimed to train a convolutional neural network (CNN) to segment and quantify tumour burden in [18F]-fluorodeoxyglucose (FDG) PET/CT images and to evaluate the association between CNN-based measurements and overall survival (OS) in patients with lung cancer. A secondary aim was to make the method available to other researchers.

Methods
A total of 320 consecutive patients referred for FDG PET/CT due to suspected lung cancer were retrospectively selected for this study. Two nuclear medicine specialists manually segmented abnormal FDG uptake in all of the PET/CT studies. One-third of the patients were assigned to a test group. Survival data were collected for this group. The CNN was trained to segment lung tumours and thoracic lymph nodes. Total lesion glycolysis (TLG) was calculated from the CNN-based and manual segmentations. Associations between TLG and OS were investigated using a univariate Cox proportional hazards regression model.

Results
The test group comprised 106 patients (median age, 76 years (IQR 61–79); n = 59 female). Both CNN-based TLG (hazard ratio 1.64, 95% confidence interval 1.21–2.21; p = 0.001) and manual TLG (hazard ratio 1.54, 95% confidence interval 1.14–2.07; p = 0.004) estimations were significantly associated with OS.

Conclusion
Fully automated CNN-based TLG measurements of PET/CT data showed were significantly associated with OS in patients with lung cancer. This type of measurement may be of value for the management of future patients with lung cancer. The CNN is publicly available for research purposes.