bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra- and interobserver reliability analysis of pediatric lower limb parameters on digital long leg radiographs
Authors: Braun Sebastian , Brenneis Marco , Holder Jana , Meurer Andrea , Stief Felix 
Published: January 2023

Abstract
Background
Malalignments of the lower extremity are common reasons for orthopedic consultation because it may lead to osteoarthritis in adulthood. An accurate and reliable radiological assessment of lower limb alignment in children and adolescents is essential for clinical decision-making on treatment of limb deformities and for regular control after a surgical intervention.

Objective
First, does the analysis of full-length standing anteroposterior radiographs show a good intra- and interobserver reliability? Second, which parameter is most susceptible to observer-dependent errors? Third, what is the Standard Error of Measurement (SEM95%) of the absolute femoral and tibial length?

Methods
Two observers evaluated digital radiographs of 144 legs from 36 children and adolescents with pathological valgus alignment before a temporary hemiepiphysiodesis and before implant removal. Parameters included Mechanical Femorotibial Angle (MFA), Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (mLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), mechanical Lateral Proximal Femoral Angle (mLPFA), mechanical Lateral Distal Tibial Angle (mLDTA), Joint Line Convergence Angle (JLCA), femur length, tibial length. Intra- and interobserver reliability (ICC2,1), SEM95% and proportional errors were calculated.

Results
The intra- and interobserver reliability for almost all measurements was found to be good to excellent (Intra-ICC2,1: 0.849–0.999; Inter-ICC2,1: 0.864–0.996). The SEM95% of both observers was found to be ± 1.39° (MFA), ± 3.31 mm (MAD), ± 1.06° (mLDFA) and ± 1.29° (mMPTA). The proportional error of MAD and MFA is comparable (47.29% vs. 46.33%). The relevant knee joint surface angles show a lower proportional error for mLDFA (42.40%) than for mMPTA (51.60%). JLCA has a proportional error of 138%. Furthermore, the SEM95% for the absolute values of the femoral and tibial length was 4.53 mm for the femur and 3.12 mm for the tibia.

Conclusions
In conclusion, a precise malalignment measurement and the knowledge about SEM95% of the respective parameters are crucial for correct surgical or nonsurgical treatment. The susceptibility to error must be considered when interpreting malalignment analysis and must be considered when planning a surgical intervention. The results of the present study elucidate that MAD and MFA are equally susceptible to observer-dependent errors. This study shows good to excellent intra- and interobserver ICCs for all leg alignment parameters and joint surface angles, except for JLCA.
Trial registration: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053.

Level of evidence
I, Diagnostic Study.
High-risk human papillomavirus genotype distribution among women with gynecology complaints in northwest Ethiopia
Authors: Derbie Awoke , Maier Melanie , Amare Bereket , Misgan Eyaya , Nibret Endalkachew , Liebert Uwe G. , Woldeamanuel Yimtubezinash , Abebe Tamrat 
Published: January 2023

Abstract
Background
Human papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities.

Methods
A health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany.

Results
We included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer.

Conclusions
HR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia.
How to dose follitropin delta for the first insemination cycle according to the ESHRE and ASRM guidelines; a retrospective cohort study
Authors: Arab Suha , Frank Russell , Ruiter Jacob , Dahan Michael H. 
Published: January 2023

Abstract
Background
Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.

Results
A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6–9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0–4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0–6.0mcg FD.

Conclusions
Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.
Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?
Authors: Gunst Jan , Casaer Michael P. , Preiser Jean-Charles , Reignier Jean , Van den Berghe Greet 
Published: January 2023

AbstractAlthough numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness.
Transcriptomic alterations underlying metaplasia into specific metaplastic components in metaplastic breast carcinoma
Authors: Lien Huang-Chun , Hsu Chia-Lang , Lu Yen-Shen , Chen Tom Wei-Wu , Chen I.-Chun , Li Yu-Chia , Huang Chiun-Sheng , Cheng Ann-Lii , Lin Ching-Hung 
Published: January 2023

Abstract
Background
Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear.

Methods
Fifty-nine NST components and paired metaplastic components (spindle carcinomatous [SPS], matrix-producing, rhabdoid [RHA], and squamous carcinomatous [SQC] components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software.

Results
Hierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial–mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-β and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis.

Conclusions
We presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.
Proteomic aptamer analysis reveals serum markers that characterize preclinical systemic sclerosis (SSc) patients at risk for progression toward definite SSc
Authors: Bellocchi Chiara , Assassi Shervin , Lyons Marka , Marchini Maurizio , Mohan Chandra , Santaniello Alessandro , Beretta Lorenzo 
Published: January 2023

AbstractBackgroundThe study of molecular mechanisms characterizing disease progression may be relevant to get insights into systemic sclerosis (SSc) pathogenesis and to intercept patients at very early stage. We aimed at investigating the proteomic profile of preclinical systemic sclerosis (PreSSc) via a discovery/validation two-step approach.MethodsSOMAcan aptamer-based analysis was performed on a serum sample of 13 PreSSc (discovery cohort) according to 2001 LeRoy and Medsger criteria (characterized solely by Raynaud phenomenon plus a positive nailfold capillaroscopy and SSc-specific antibodies without any other sign of definite disease) and 8 healthy controls (HCs) age, gender, and ethnicity matched. Prospective data were available up to 4±0.6 years to determine the progression to definite SSc according to the EULAR/ACR 2013 classification criteria. In proteins with relative fluorescence units (RFU) > |1.5|-fold vs HCs values, univariate analysis was conducted via bootstrap aggregating models to determine the predicting accuracy (progression vs non-progression) of categorized baseline protein values. Gene Ontologies (GO terms) and Reactome terms of significant proteins at the adjusted 0.05 threshold were explored. Significant proteins from the discovery cohort were finally validated via ELISAs in an independent validation cohort of 50 PreSSc with clinical prospective data up to 5 years. Time-to-event analysis for interval-censored data was used to evaluate disease progression.ResultsIn the discovery cohort, 286 out of 1306 proteins analyzed via SomaScan, were differentially expressed versus HCs. Ten proteins were significantly associated with disease progression; analysis through GO and Reactome showed differentially enriched pathways involving angiogenesis, endothelial cell chemotaxis, and endothelial cell chemotaxis to fibroblast growth factor (FGF). In the validation cohort, endostatin (HR=10.23, CI95=2.2–47.59,p=0.003) was strongly associated with disease progression, as well as bFGF (HR=0.84, CI95=0.709-0.996,p=0.045) and PAF-AHβ (HR=0.372, CI95=0.171–0.809,p=0.013)ConclusionsA distinct protein profile characterized PreSSc from HCs and proteins associated with hypoxia, vasculopathy, and fibrosis regulation are linked with the progression from preclinical to definite SSc. These proteins, in particular endostatin, can be regarded both as markers of severity and molecules with pathogenetic significance as well as therapeutic targets.
A case of doxorubicin and cyclophosphamide therapy-induced type 1 diabetes: a case report
Authors: Miyabayashi Makoto , Onishi Shunichiro , Yoshida Tomohiko , Takemoto Minoru 
Published: January 2023

Abstract
Background
Patients receiving immune checkpoint inhibitors have been reported to develop autoimmune endocrine diseases, including type 1 diabetes, although few drugs have been shown to induce type 1 diabetes. Additionally, it is important to note that drugs other than immune checkpoint inhibitors could lead to the development of type 1 diabetes.

Case presentation
A 54-year-old Filipino female patient underwent surgery for left-sided breast cancer. Postoperative chemotherapy was initiated, including doxorubicin (Adriamycin) and cyclophosphamide therapy. The patient was brought to our hospital by ambulance after consciousness disturbance following three courses of doxorubicin and cyclophosphamide therapy and was hospitalized. Her blood glucose and hemoglobin A1c levels were 1661 mg/dL and 11.9%, respectively. The patient was diagnosed with diabetic ketoacidosis after arterial blood gas analysis indicated a blood pH of 7.120. Her insulin secretion was impaired, and her anti-glutamic acid decarboxylase antibody test result was significantly positive.

Conclusions
The present case shows that doxorubicin and cyclophosphamide therapy may cause unexpected adverse responses, such as type 1 diabetes, though rarely, and highlights the importance of careful patient follow-up. This report is the first to present a case of type 1 diabetes that suddenly developed after doxorubicin and cyclophosphamide treatment.
Effect of logging residue removal and mechanical site preparation on productivity of the subsequent Scots pine (Pinus sylvestris L.) stands
Authors: Węgiel Andrzej , Jakubowski Jakub , Molińska-Glura Marta , Polowy Krzysztof , Węgiel Jolanta , Gornowicz Roman 
Published: January 2023

Abstract
Key message
Removal of logging residue negatively affected tree diameter and height, but had no significant effect on the basal area of the subsequent stand (in the mid-term). On the other hand, different methods of mechanical site preparation (bedding, plowing furrows, and trenching) had no effect on tree growth 1 year after planting, but had a significant effect on tree diameter, tree height, and basal area in the mid-term. Bedding treatments could have a significant positive impact on the productivity of the subsequent Scots pine stands, even when planted on sandy, free-draining soils.

Context
Increased use of logging residues in forests may address the growing demand for renewable energy. However, concerns have arisen regarding the depletion of the forest soil, resulting in a decrease in the productivity of the next forest generation. Identifying the drivers of forest growth may be the key to understanding the relationship between logging residue removal and stand productivity.

Aims
Quantifying the effect of three mechanical site preparation methods (bedding, plowing furrows, and trenching) combined with five methods of logging residue management (complete removal, comminution, incineration, leaving whole, comminution with, and without mixing with topsoil) on growth of subsequent Scots pine stands, 1 year and 12 years after planting.

Methods
The experiment was set up as a randomized complete block design of 45 plots with three replications of combinations of three mechanical site preparation methods and five logging residue treatment methods.

Results
The effects of the different methods of mechanical site preparation were not significant 1 year after planting but bedding treatment caused increase in DBH, tree height, and basal area after 12 years. Various methods of logging residue management did not cause any differences in the survival rate nor the basal area of the next-generation stands; however, there was a significant influence on tree sizes. Moreover, the effects changed with time; in plots with a complete removal of logging residues, the trees were the highest 1 year after planting, but after 12 years, their height and DBH were the lowest.

Conclusions
It can be concluded that bedding treatments could have a significant positive impact on the productivity of the subsequent Scots pine stands. No effect found of different logging residue treatments on the productivity of Scots pine stands further confirms that the increased removal of biomass from the forest environment does not necessarily result in its rapid degradation. Observations at longer term are however needed to obtain the full spectrum of responses to logging residue removal.
Screening for opioid use disorder and co-occurring depression and post-traumatic stress disorder in primary care in New Mexico
Authors: Murray-Krezan Cristina , Dopp Alex , Tarhuni Lina , Carmody Mary D. , Becker Kirsten , Anderson Jessica , Komaromy Miriam , Meredith Lisa S. , Watkins Katherine E. , Wagner Katherine , Page Kimberly ,   the CLARO Study Group
Published: January 2023

Abstract
Background
Identifying patients in primary care services with opioid use disorder and co-occurring mental health disorders is critical to providing treatment. Objectives of this study were to (1) assess the feasibility of recruiting people to screen in-person for opioid use disorder and co-occurring mental health disorders (depression and/or post-traumatic stress disorder) in primary care clinic waiting rooms in preparation for a randomized controlled trial, and (2) compare results of detecting these disorders by universal in-person screening compared to electronic health record (EHR) diagnoses.

Methods
This cross-sectional feasibility and pilot study recruited participants from four primary care clinics, two rural and two urban, from three health care organizations in New Mexico. Inclusion criteria were adults (≥ 18 years), attending one of the four clinics as a patient, and who spoke English or Spanish. Exclusion criteria were people attending the clinic for a non-primary care visit (e.g., dental, prescription pick up, social support). The main outcomes and measures were (1) recruitment feasibility which was assessed by frequencies and proportions of people approached and consented for in-person screening, and (2) relative differences of detecting opioid use disorder and co-occurring mental health disorders in waiting rooms relative to aggregate EHR data from each clinic, measured by prevalence and prevalence ratios.

Results
Over two-weeks, 1478 potential participants were approached and 1145 were consented and screened (77.5% of patients approached). Probable opioid use disorder and co-occurring mental health disorders were identified in 2.4% of those screened compared to 0.8% in EHR. Similarly, universal screening relative to EHR identified higher proportions of probable opioid use disorder (4.5% vs. 3.4%), depression (17.5% vs. 12.7%) and post-traumatic stress disorder (19.0% vs. 3.6%).

Conclusions
Universal screening for opioid use disorder, depression, and post-traumatic stress disorder was feasible, and identified three times as many patients with these co-occurring disorders compared to EHR. Higher proportions of each condition were also identified, especially post-traumatic stress disorder. Results support that there are likely gaps in identification of these disorders in primary care services and demonstrate the need to better address the persistent public health problem of these co-occurring disorders.