bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling pathways, microenvironment, and targeted treatments in Langerhans cell histiocytosis
Authors: Gao Xue-min , Li Jian , Cao Xin-xin 
Published: December 2022

AbstractLangerhans cell histiocytosis (LCH) is an inflammatory myeloid malignancy in the “L-group” histiocytosis. Mitogen-activated protein kinase (MAPK) pathway activating mutations are detectable in nearly all LCH lesions. However, the pathogenic roles of MAPK pathway activation in the development of histiocytosis are still elusive. This review will summarize research concerning the landscape and pathogenic roles of MAPK pathway mutations and related treatment opportunities in Langerhans cell histiocytosis.
Association between genetic risk score and tri-ponderal mass index growth trajectories among different dietary consumption adolescents in a prospective Taiwanese cohort
Authors: Wu Yi-Fan , Chien Kuo-Liong , Chen Yang-Ching 
Published: December 2022

Abstract
Background
Single-nucleotide polymorphisms (SNPs) in various genetic loci are associated with childhood obesity; however, their influence on adolescent growth patterns has rarely been explored. This study investigated whether genetic variants could predict tri-ponderal mass index (TMI)-derived growth trajectories and the interaction between genetic and dietary factors.

Methods
We conducted Taiwan Puberty Longitudinal Study, a prospective cohort that recruited 1,135 children since 2018. Anthropometric measurements were recorded every three months, while dietary nutrition assessment and biological sampling for genotyping were collected during the first visit. TMI growth trajectory groups were identified using growth mixture modeling. A multinomial logistic regression model for different growth trajectories was used to examine the effect of candidate SNPs, and the most related SNPs were used to establish the genetic risk score. We then explored the effect of the genetic risk score in subgroup analysis according to dietary calories and different dietary consumption patterns.

Results
Three TMI-based growth trajectory groups were identified among adolescents. The “increased weight” trajectory group accounted for approximately 9.7% of the participants. FTO/rs7206790 was associated with the increased weight growth trajectory after adjusting for the baseline TMI and other correlated covariates (OR: 2.13, 95% CI: 1.08–4.21). We generated the genetic risk score using 4 SNPs (FTO/rs7206790, ADCY9/rs2531995, TFAP2B/rs4715210, and TMEM18/rs6548238) and selected the threshold of 10 points to define risk categories. There were 11.66% and 3.24% of participants belonged to the increased weight trajectory in high- and low-risk groups, respectively; and the predictive ability of the genetic risk score was notable among low calories intake participants (OR: 1.90, 95% CI: 1.18–3.05 vs. OR: 1.17, 95% CI: 0.78–1.75 in high calories intake group).

Conclusion
Our results offer a new perspective on the genetic and dietary basis of changes in adolescent obesity status. Individualized interventions for obesity prevention may be considered among high-risk children.
Database coverage and their use in systematic reviews regarding spinal manipulative therapy: an exploratory study
Authors: Eybye Martin Nørregård , Madsen Simon Dyrløv , Schultz Anders Nikolai Ørsted , Nim Casper Glissmann 
Published: December 2022

Abstract
Background
Systematic reviews (SRs) of randomized controlled trials (RCTs) are considered one of the most reliable study types. Through a systematic and thorough literature search, researchers aim to collect all research relevant to their purpose. The selection of databases can be challenging and depend on the topic of interest. The Cochrane Handbook suggests searching at least the following three databases: Cochrane Library, MEDLINE, and EMBASE. However, this is not always sufficient for reviews on the musculoskeletal field in general.

This study aimed to examine the frequency and choice of databases used by researchers in SRs of spinal manipulative therapy (SMT). Secondly, to analyze the RCTs included in the SRs to determine the optimal combination of databases needed to conduct efficient literature searches for SRs of SMT.

Methods
SRs investigating the effect of SMT on any patient-reported outcome measure were identified through searches in PubMed and Epistemonikos (all entries till date of search February 25, 2022). For each SR, databases searched and included RCTs were collected. RCTs were searched individually in nine databases (Cochrane Library, MEDLINE/PubMed, EMBASE, Google Scholar, CINAHL, Web of Science, Index to Chiropractic Literature, PEDro, and AMED). Coverage rates were calculated using the number of retrieved RCTs by the database or combinations of databases divided by the total number of RCTs.

Results
Eighty-five SRs published met the inclusion criteria, and 442 unique RCTs were retrieved. The most frequently searched database was MEDLINE/PubMed. Cochrane Library had the highest overall coverage rate and contained the third most unique RCTs. While a 100% retrieval was not possible, as 18 RCTs could not be retrieved in any of the nine databases, the combination of Cochrane Library, Google Scholar, and PEDro retrieved all possible RCTs with a combined coverage rate of 95.9%.

Conclusions
For SRs on SMT, we recommend using the combination suggested by the Cochrane Handbook of Cochrane Library, MEDLINE/PubMed, Embase, and in addition, PEDro and Index to Chiropractic Literature. Google Scholar might be used additionally as a tool for searching gray literature and quality assurance.
Information and BMI limits for patients with obesity eligible for knee arthroplasty: the Swedish surgeons’ perspective from a nationwide cross-sectional study
Authors: Ighani Arani Perna , Wretenberg Per , W-Dahl Annette 
Published: December 2022

Abstract
Background
In the past decades, the incidence of obesity has increased worldwide. This disease is often accompanied with several comorbidities and therefore, surgeons and anesthesiologists should be prepared to provide optimal management for these patients. The aim of this descriptive cross-sectional study was to map the criteria and routines that are used by Swedish knee arthroplasty surgeons today when considering patients with obesity for knee arthroplasty.

Methods
A survey including 21 items was created and sent to all the Swedish centers performing knee arthroplasty. The survey included questions about the surgeons’ experience, hospital routines of preoperative information given and the surgeons’ individual assessment of patients with obesity that candidates for knee arthroplasty. Descriptive statistics were used to present the data.

Results
A total of 203 (64%) knee surgeons responded to the questionnaire. Almost 90% of the surgeons claimed to inform their patients with obesity that obesity has been associated with an increased risk of complications after knee arthroplasty. Seventy-nine percent reported that they had an upper BMI limit to perform knee arthroplasty, a larger proportion of the private centers had a BMI limit compared to public centers. The majority of the centers had an upper BMI limit of 35.

Conclusion
The majority of the knee arthroplasty surgeons in Sweden inform their patients with obesity regarding risks associated with knee arthroplasty. Most centers that perform knee arthroplasties in Sweden have an upper BMI limit.
Incidence and treatment outcomes of Graves’ disease in Thailand: a single-center retrospective observational study
Authors: Kanokwongnuwat Wasit , Penpong Nawarat , Sangsri Chaninporn 
Published: December 2022

Abstract
Background
Treatment patterns and outcomes of Graves’ disease (GD) are variable around the world. However, studies on treatment outcomes of GD from the Asian populations are limited. We aimed to evaluate treatment outcomes of GD in Thailand.

Methods
Patients with new diagnoses of GD in a single center between 2014–2018 were retrospectively reviewed. The diagnosis of GD was based on clinical features, which included diffuse goiter, Graves’ orbitopathy (GO), pretibial myxedema and acropachy.

Results
The age-adjusted incidence of GD was 26.57 per 100,000 per year. The study included 355 patients aged 15 years or above with a follow-up period of at least 24 months. Antithyroid drug (ATD) was the most popular first-line treatment modality with 98.7% patients receiving the treatment, followed by radioactive iodine (RAI) treatment in 1.3% patients. The most effective treatment modality was surgery with a remission rate of 100%. ATD had a lowest remission rate of 23.8%. Multivariable Cox regression analysis showed GO (HR 1.76, 95% CI 1.08–2.88) and initial TSH < 0.01 uIU/ml (HR 1.61, 95% CI 1.14–2.28) were significant factors associated with an increased treatment failure rate.

Conclusion
Treatment failure with ATD in patients with GD was frequent in this population. The diagnosis of GD based solely on clinical features may explain the high treatment failure rate in this study. More definitive treatment could be used to prevent relapse and complications of the disease.
Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: results of a prospective cohort study
Authors: Dick Julia , Tüchler Anja , Brédart Anne , Vitinius Frank , Wassermann Kirsten , Rhiem Kerstin , Schmutzler Rita K. 
Published: December 2022

AbstractBackgroundWomen carryingBRCA1/2pathogenic variants are exposed to elevated risks of developing breast cancer (BC) and are faced by a complex decision-making process on preventative measures, i.e., risk-reducing mastectomy (RRM), and intensified breast surveillance (IBS). In this prospective cohort study we investigated the effect of anxiety, personality factors and coping styles on the decision-making process on risk management options in women with pathogenic variants inBRCA1/2.MethodsBreast cancer unaffected and affected women with a pathogenic variant in theBRCA1orBRCA2gene were psychologically evaluated immediately before (T0), 6 to 8 weeks (T1) and 6 to 8 months (T2) after the disclosure of their genetic test results. Uptake of RRM and IBS was assessed at T2. Psychological data were gathered using questionnaires on risk perception, personality factors, coping styles, decisional conflict, depression and anxiety, including the Hospital Anxiety and Depression Scale (HADS). We performed tests on statistical significance and fitted a logistic regression based on significance level.ResultsA total of 98 women were included in the analysis. Baseline anxiety levels in women opting for RRM were high but decreased over time, while they increased in women opting for intensified breast surveillance (IBS). Elevated levels of anxiety after genetic test result disclosure (T1) were associated with the decision to undergo RRM (p < 0.01; OR = 1.2, 95% CI = 1.05–1.42), while personal BC history and personality factors seemed to be less relevant.ConclusionsConsidering psychosocial factors influencing the decision-making process of women with pathogenic variants inBRCA1/2may help improving their genetic and psychological counselling. When opting for IBS they may profit from additional medical and psychological counselling.Trial registrationRetrospectively registered at the German Clinical Trials Register underDRKS00027566on January 13, 2022.
Childhood adiposity, serum metabolites and breast density in young women
Authors: Dorgan Joanne F. , Baer Heather J. , Bertrand Kimberly A. , LeBlanc Erin S. , Jung Seungyoun , Magder Laurence S. , Snetselaar Linda G. , Stevens Victor J. , Zhang Yuji , Van Horn Linda 
Published: December 2022

AbstractBackgroundChildhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density.MethodsLongitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI)z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography–tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25–29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMIz-scores and breast density, and the R packagemediationwas used to quantify mediation.ResultsOf the 115 metabolites associated with BMIz-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46;P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26;P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18;P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity–%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV.ConclusionsAdditional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.
Rectal leiomyosarcoma as the initial phenotypic manifestation of Li–Fraumeni-like syndrome: a case report and review of the literature
Authors: Severino Natalia Parisi , Waisberg Jaques , Fragoso Maria Candida Barisson Villares , de Lima Luiz Guilherme Cernaglia Aureliano , Balsamo Flavia , Henriques Alexandre Cruz , Bianco Bianca , de Sousa Gehrke Flávia 
Published: December 2022

Abstract
Background
Leiomyosarcoma is a rare malignant tumor of smooth muscle origin and represents 10–20% of all soft tissue sarcomas. Primary colon and rectal sarcomas constitute < 0.1% of all large bowel malignancies. In Li–Fraumeni syndrome, sarcomas are the second most frequent cancer (25%). Li–Fraumeni syndrome is a genetic disease with a familial predisposition to multiple malignant neoplasms. This syndrome has an autosomal dominant pattern of inheritance and high penetrance characterized by germline TP53 mutations. Patients with a history of cancer who do not meet all the “classic” criteria for Li–Fraumeni syndrome are considered to have Li–Fraumeni-like syndrome. To the best of our knowledge, this article is the first report of a patient with rectal leiomyosarcoma as the initial phenotypic manifestation of Li–Fraumeni-like syndrome. The authors also present a literature review.

Case presentation
A 67-year-old Brazilian woman underwent anterior rectosigmoidectomy and panhysterectomy secondary to rectal leiomyosarcoma. She subsequently developed carcinomatosis and died 2 years after the operation. Her family medical history consisted of a daughter who died at 32 years of age from breast cancer, a granddaughter diagnosed with adrenocortical carcinoma at 6 years of age and two siblings who died from prostate cancer. A genetic study was carried out to identify a pathogenic variant of Li–Fraumeni syndrome. In the DNA extracted from the peripheral blood leukocyte, restriction fragment length polymorphism was analyzed to search for mutations in the TP53 gene. The DNA sequencing identified the germline pathogenic variant p. R337H heterozygous in exon 10 of TP53. The patient was classified as having Li–Fraumeni-like syndrome.

Conclusion
In patients with rectal leiomyosarcoma, it is advisable to investigate the family history of cancer and perform genetic studies to screen for Li–Fraumeni syndrome.
Relationships between uptake of [68Ga]Ga-DOTA-TATE and absorbed dose in [177Lu]Lu-DOTA-TATE therapy
Authors: Stenvall Anna , Gustafsson Johan , Larsson Erik , Roth Daniel , Sundlöv Anna , Jönsson Lena , Hindorf Cecilia , Ohlsson Tomas , Sjögreen Gleisner Katarina 
Published: December 2022

Abstract
Background
Somatostatin receptor 68Ga PET imaging is standard for evaluation of a patient’s suitability for 177Lu peptide receptor radionuclide therapy of neuroendocrine tumours (NETs). The 68Ga PET serves to ensure sufficient somatostatin receptor expression, commonly evaluated qualitatively. The aim of this study is to investigate the quantitative relationships between uptake in 68Ga PET and absorbed doses in 177Lu therapy.

Method
Eighteen patients underwent [68Ga]Ga-DOTA-TATE PET imaging within 20 weeks prior to their first cycle of [177Lu]Lu-DOTA-TATE. Absorbed doses for therapy were estimated for tumours, kidney, spleen, and normal liver parenchyma using a hybrid SPECT/CT–planar method. Gallium-68 activity concentrations were retrieved from PET images and also used to calculate SUVs and normalized SUVs, using blood and tissue for normalization. The 68Ga activity concentrations per injected activity, SUVs, and normalized SUVs were compared with 177Lu activity concentrations 1 d post-injection and 177Lu absorbed doses. For tumours, for which there was a variable number per patient, both inter- and intra-patient correlations were analysed. Furthermore, the prediction of 177Lu tumour absorbed doses based on a combination of tumour-specific 68Ga activity concentrations and group-based estimates of the effective half-lives for grade 1 and 2 NETs was explored.

Results
For normal organs, only spleen showed a significant correlation between the 68Ga activity concentration and 177Lu absorbed dose (r = 0.6). For tumours, significant, but moderate, correlations were obtained, with respect to both inter-patient (r = 0.7) and intra-patient (r = 0.45) analyses. The correlations to absorbed doses did not improve when using 68Ga SUVs or normalized SUVs. The relationship between activity uptakes for 68Ga PET and 177Lu SPECT was stronger, with correlation coefficients r = 0.8 for both inter- and intra-patient analyses. The 177Lu absorbed dose to tumour could be predicted from the 68Ga activity concentrations with a 95% coverage interval of − 65% to 248%.

Conclusions
On a group level, a high uptake of [68Ga]Ga-DOTA-TATE is associated with high absorbed doses at 177Lu-DOTA-TATE therapy, but the relationship has a limited potential with respect to individual absorbed dose planning. Using SUV or SUV normalized to reference tissues do not improve correlations compared with using activity concentration per injected activity.
VHL-recruiting PROTAC attenuates renal fibrosis and preserves renal function via simultaneous degradation of Smad3 and stabilization of HIF-2α
Authors: Yang Jiayi , Ruan Yuyi , Wang Dan , Fan Jinjin , Luo Ning , Chen Huiting , Li Xiaoyan , Chen Wei , Wang Xin 
Published: December 2022

Abstract
Background
Renal fibrosis is the pathological foundation of various chronic kidney diseases progressing to end stage renal failure. However, there are currently no nephroprotective drugs targeted to the fibrotic process in clinical practice. Proteolytic targeting chimeras (PROTACs), which reversibly degrade target proteins through the ubiquitin–proteasome pathway, is a novel therapeutic modality. Smad3 is a key pathogenic factor in fibrogenesis while HIF-2α exhibits prominent renal protective effects, which is the natural substrate of von Hippel–Lindau (VHL) E3 Ligase. We hypothesied the construction of VHL-recruiting, Smad3-targeting PROTAC might combine the effects of Smad3 degradation and HIF-2α stabilization, which not only improving the clinical efficacy of PROTAC but also avoiding its potential off-target effects, could greatly improve the possibility of its translation into clinical drugs.

Methods
By joining the Smad3-binding small molecule compound (SMC) to VHL-binding SMC with a linker, we designed and synthesized a Smad3-targeting, VHL-based PROTAC. The effects of this PROTAC on targeted proteins were verified both in vitro and in vivo. The toxicity and pharmacokinetic (PK) evaluations were conducted with both male and female mice. The renal protection effects and mechanism of PROTAC were evaluated in unilateral ureteral obstruction (UUO) and 5/6 subtotal nephrectomy (5/6Nx) mouse model.

Results
By optimizing the linker and the Smad3-binding SMC, we got a stable and high efficient PROTAC which simultaneously degraded Smad3 and stabilized HIF-2α both in vivo and in vitro. The acute toxicity evaluation showed a pretty large therapeutic window of the PROTAC. The prominent renal protection effects and its underlying mechanism including anti-fibrosis and anti-inflammatory, improving renal anemia and promoting kidney repair, had all been verified in UUO and 5/6Nx mouse model.

Conclusion
By accurate combination of PROTAC targeted protein and E3 ligase, we got a Smad3-targeting, VHL-recruting PROTAC which caused Smad3 degradation and HIF-2α stabilization effects simultaneously, and led to the strong renal function protection effects.
Green route synthesis and characterization of β-Bi2O3/SiO2 and β-Bi2O3/Bi2O2.75/SiO2 using Juglans regia L. shell aqueous extract and photocatalytic properties for the degradation of RB-5
Authors: Yañez-Cruz Maria Guadalupe , Villanueva-Ibáñez Maricela , Méndez-Arriaga Fabiola , Lucho-Constantino Carlos Alexander , Hernández-Pérez María de los Ángeles , Ramírez-Vargas María del Rocío , Flores-González Marco Antonio 
Published: December 2022

Abstract
Background
Photocatalyst oxides added with silicon improve their photocatalytic properties. In this research, nanostructured β-Bi2O3/SiO2 and β-Bi2O3/Bi2O2.75/SiO2 were obtained by means of a green method mediated by the using the aqueous extract of J. regia shell as the source of reducing biomolecules and as a natural source of plant silicon.

Method
The β-Bi2O3/SiO2 and β-Bi2O3/Bi2O2.75/SiO2 nanostructures were characterized by Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray diffraction, high-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy, X-ray photoelectron spectroscopy (XPS), ultraviolet–visible diffuse reflectance spectroscopy (UV–Vis DRS), and photoluminescence spectroscopy. The photocatalytic activity was measured by the degradation of Reactive Black 5 dye (RB-5).

Results
FT-IR and XPS demonstrated the presence of plant silicon in the bismuth oxide photocatalysts. HR-TEM showed that the crystal size of the as-synthesized materials is ~ 25 nm and revealed that the β-Bi2O3 synthesized with ground shell extract and heat-treated at 300 °C contains the Bi2O2.75 phase. Good photocatalytic activity was found in all the studied materials; particularly, the heat-treated nanostructures showed excellent properties resulting in 92% degradation of RB-5 under UV–Vis light after 15 min of exposure, and 98% after 180 min.

Conclusions
The findings of this research suggest that the metabolites coating the Bi2O3, which generate a large amount of hydroxyl radicals, the plant silicon content, and the crystalline defects conferred by the synthesis medium, all contribute to the improved degradation of the azo dye, providing the nanostructures with better photocatalytic activity.