bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of acetabular cup placement during anterolateral supine total hip arthroplasty using intraoperative fluoroscopy: a retrospective study
Authors: Cho Eiji , Hisatome Takashi , Oda Shuhei , Fujimaki Hirohisa , Nakanishi Kazuyoshi 
Published: December 2022

Abstract
Background
In our institution, total hip arthroplasty (THA) is performed using the anterolateral supine (ALS) approach with intraoperative fluoroscopy. This study aimed to investigate and review the accuracy of acetabular cup placement in ALS-THA using intraoperative fluoroscopy.

Methods
A total of 142 patients with 154 joints (mean age 64.3 years, 30 males and 112 females) underwent ALS-THA with intraoperative fluoroscopy at the same institution. The target angle of the cup position was set at 40° for radiographic inclination (RI) and 5°–25° for radiographic anteversion (RA) based on the functional pelvic plane according to the pelvic motion during individual postural changes. The cup position angle was measured using postoperative computed tomography, and the error in the target angle was investigated.

Results
The target angle of RI was 40°, and the postoperative RI was 39.3° ± 4.3°. The target angle of the RA was 17° ± 2.6°, and the postoperative RA was 20.6° ± 3.7°. The absolute values of the error from the target angle were 3.6° ± 2.5° for RI and 4.2° ± 3.3° for RA.
For RI and RA, 67.5% (104/154 joints) were within ± 5° of the target and 96.1% (148/154 joints) were within ± 10°.

Conclusions
The accuracy of cup positioning in ALS-THA using intraoperative fluoroscopy was good and appeared comparable to that of various navigation systems.
Successful management of hemodynamic instability secondary to saddle pulmonary embolism-induced cardiac arrest using VA-ECMO in advanced malignancy with brain metastases
Authors: Pan Jianneng , Zhou Xiaoyang , Xu Zhaojun , Chen Bixin 
Published: December 2022

Abstract
Background
Saddle pulmonary embolism (SPE) represents a rare type of venous thromboembolism that frequently causes circulation collapse and sudden death. While venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been well established as a salvage treatment for SPE-induced circulatory shock, it is infrequently administered in patients with advanced malignancy, especially those with brain metastases, given the potential bleeding complications and an uncertain prognosis. As far, there are rare case reports regarding the successful management of hemodynamic instability secondary to SPE-induced cardiac arrest using VA-ECMO in advanced malignancy patients with brain metastases.

Case presentation
A 65-year-old woman presenting with cough and waist discomfort who had a history of lung cancer with brain metastases was admitted to the hospital to receive chemoradiotherapy. She suffered sudden cardiac arrest during hospitalization and returned to spontaneous circulation after receiving a 10-min high-quality cardiopulmonary resuscitation. Pulmonary embolism was suspected due to the collapsed hemodynamics and a distended right ventricle identified by echocardiography. Subsequent computed tomographic pulmonary angiography revealed a massive saddle thrombus straddling the bifurcation of the pulmonary trunk. VA-ECMO with adjusted-dose systemic heparinization was initiated to rescue the unstable hemodynamics despite receiving thrombolytic therapy with alteplase. Immediately afterward, the hemodynamic status of the patient stabilized rapidly. VA-ECMO was successfully discontinued within 72 h of initiation without any clotting or bleeding complications. She was weaned off invasive mechanical ventilation on the 6th day of intensive care unit (ICU) admission and discharged from the ICU 3 days later with good neurological function.

Conclusion
VA-ECMO may be a ‘bridging’ therapy to circulation recovery during reperfusion therapy for SPE-induced hemodynamic collapse in malignancy patients with brain metastases.
Systemic amyloidosis journey from diagnosis to outcomes: a twelve-year real-world experience of a single center in a middle-income country
Authors: Szor Roberta Shcolnik , Fernandes Fabio , Lino Angelina Maria Martins , Mendonça Leonardo Oliveira , Seguro Fernanda Salles , Feitosa Valkercyo Araujo , Castelli Jussara Bianchi , Jorge Lecticia Barbosa , de Oliveira Alves Lucas Bassolli , de Menezes Neves Precil Diego Miranda , de Oliveira Souza Evandro , Cavalcante Livia Barreira , Malheiros Denise , Kalil Jorge , Martinez Gracia Aparecida , Rocha Vanderson 
Published: December 2022

Abstract
Background
Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients´ medical records were retrospectively reviewed.

Results
One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, ≥ 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had ≥ 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I–II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG ≥ 2 were identified as independent risk factors for reduced survival.

Conclusions
Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries.
Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping
Authors: Pi Chenghui , Tang Wenjing , Li Zhishuai , Liu Yang , Jing Qi , Dai Wei , Wang Tao , Yang Chunxiao , Yu Shengyuan 
Published: December 2022

Abstract
Background
Cortical spreading depression (CSD) is an electrophysiological event underlying migraine aura. Traditional CSD models are invasive and often cause injuries. The aim of the study was to establish a minimally invasive optogenetic CSD model and identify the active networks after CSD using whole-brain activity mapping.

Methods
CSD was induced in mice by light illumination, and their periorbital thresholds and behaviours in the open field, elevated plus-maze and light-aversion were recorded. Using c-fos, we mapped the brain activity after CSD. The whole brain was imaged, reconstructed and analyzed using the Volumetric Imaging with Synchronized on-the-fly-scan and Readout technique. To ensure the accuracy of the results, the immunofluorescence staining method was used to verify the imaging results.

Results
The optogenetic CSD model showed significantly decreased periorbital thresholds, increased facial grooming and freezing behaviours and prominent light-aversion behaviours. Brain activity mapping revealed that the somatosensory, primary sensory, olfactory, basal ganglia and default mode networks were activated. However, the thalamus and trigeminal nucleus caudalis were not activated.

Conclusions
Optogenetic CSD model could mimic the behaviours of headache and photophobia. Moreover, the optogenetic CSD could activate multiple sensory cortical regions without the thalamus or trigeminal nucleus caudalis to induce cortical pain.
Complexity of progranulin mechanisms of action in mesothelioma
Authors: Ventura Elisa , Xie Christopher , Buraschi Simone , Belfiore Antonino , Iozzo Renato V. , Giordano Antonio , Morrione Andrea 
Published: December 2022

Abstract
Background
Mesothelioma is an aggressive disease with limited therapeutic options. The growth factor progranulin plays a critical role in several cancer models, where it regulates tumor initiation and progression. Recent data from our laboratories have demonstrated that progranulin and its receptor, EphA2, constitute an oncogenic pathway in bladder cancer by promoting motility, invasion and in vivo tumor formation. Progranulin and EphA2 are expressed in mesothelioma cells but their mechanisms of action are not well defined. In addition, there are no data establishing whether the progranulin/EphA2 axis is tumorigenic for mesothelioma cells.

Methods
The expression of progranulin in various mesothelioma cell lines derived from all major mesothelioma subtypes was examined by western blots on cell lysates, conditioned media and ELISA assays. The biological roles of progranulin, EphA2, EGFR, RYK and FAK were assessed in vitro by immunoblots, human phospho-RTK antibody arrays, pharmacological (specific inhibitors) and genetic (siRNAs, shRNAs, CRISPR/Cas9) approaches, motility, invasion and adhesion assays. In vivo tumorigenesis was determined by xenograft models. Focal adhesion turnover was evaluated biochemically using focal adhesion assembly/disassembly assays and immunofluorescence analysis with focal adhesion-specific markers.

Results
In the present study we show that progranulin is upregulated in various mesothelioma cell lines covering all mesothelioma subtypes and is an important regulator of motility, invasion, adhesion and in vivo tumor formation. However, our results indicate that EphA2 is not the major functional receptor for progranulin in mesothelioma cells, where progranulin activates a complex signaling network including EGFR and RYK. We further characterized progranulin mechanisms of action and demonstrated that progranulin, by modulating FAK activity, regulates the kinetic of focal adhesion disassembly, a critical step for cell motility.

Conclusion
Collectively, our results highlight the complexity of progranulin oncogenic signaling in mesothelioma, where progranulin modulate functional cross-talks between multiple RTKs, thereby suggesting the need for combinatorial therapeutic approaches to improve treatments of this aggressive disease.
Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women’s Health Study: a case–case analysis
Authors: Davis Lynn Brittny C. , Lord Brittany D. , Cora Renata , Pfeiffer Ruth M. , Lawrence Scott , Zirpoli Gary , Bethea Traci N. , Palmer Julie R. , Gierach Gretchen L. 
Published: December 2022

Abstract
Background
Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm2, TDLU span (µm), and number of acini/TDLU, and that these metrics may be elevated in the normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. It is unknown whether this relationship exists in Black women, who have the highest incidence of TN breast cancer and the highest overall breast cancer mortality rate. We examined relationships between TDLU metrics and breast cancer molecular subtype among breast cancer cases in the Black Women’s Health Study (BWHS).

Methods
We assessed quantitative TDLU metrics (TDLU count/100mm2, TDLU span (µm), and number of acini/TDLU) in digitized 247 hematoxylin and eosin-stained adjacent normal tissue sections from 223 BWHS breast cancer cases, including 65 triple negative (TN) cancers (estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor-2 (HER2) negative) and 158 luminal A cancers (ER positive, HER2 negative). We evaluated associations of least square mean TDLU metrics adjusted for age and body mass index (BMI) with patient and clinical characteristics. In logistic regression models, we evaluated associations between TDLU metrics and breast cancer subtype, adjusting for age, BMI, and tumor size.

Results
Older age and higher BMI were associated with lower TDLU metrics and larger tumor size and lymph node invasion with higher TDLU metrics. The odds of TN compared with luminal A breast cancer increased with increasing tertiles of TDLU metrics, with odds ratios (95% confidence intervals) for tertile 3 versus tertile 1 of 2.18 (0.99, 4.79), 2.77 (1.07, 7.16), and 1.77 (0.79, 3.98) for TDLU count, TDLU span, and acini count/TDLU, respectively.

Conclusion
Associations of TDLU metrics with breast cancer subtypes in the BWHS are consistent with previous studies of White and Asian women, demonstrating reduced TDLU involution in TN compared with luminal A breast cancers. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype.
Testing an attachment- and trauma-informed intervention approach for parents and young children after interparental violence: protocol for a randomized controlled trial
Authors: van der Asdonk Sabine , Kesarlal Ashwina R. , Schuengel Carlo , Draaisma Nina , de Roos Carlijn , Zuidgeest Karine , Rippe Ralph C. A. , Alink Lenneke R. A. 
Published: December 2022

Abstract
Background
Interparental violence has persistent adverse effects on victimized parents and children. Young children, including infants and toddlers, are at particular risk to develop long-lasting negative outcomes, and yet specific evidence on effective intervention approaches for this vulnerable group is still lacking. This study will test the effectiveness of an attachment- and trauma-informed intervention approach in a sample of parent-child dyads who have experienced severe interparental violence. We test the individual and combined effects of two interventions: (1) “Nederlandse Interventie Kortdurend op Atypisch oudergedrag” (NIKA; Dutch, short-term intervention focused on atypical parenting behavior) aimed at improving the attachment relationship and (2) eye movement desensitization and reprocessing (EMDR) therapy aimed at reducing parental post-traumatic stress disorder (PTSD) symptoms.

Methods
This study uses a multicenter randomized controlled design across multiple domestic violence shelters in the Netherlands. We aim to recruit 150 parent-child dyads with children aged between 0.5 and 6 years old. The study design consists of two phases. During the first phase for testing the effect of NIKA only, eligible dyads are randomly allocated to either NIKA or a waitlist usual care group. A pre-test is conducted prior to the treatment period and a post-test takes place directly afterwards (6 weeks after the pre-test). Phase 2 follows directly for testing the effects of EMDR and the combination of NIKA and EMDR. Parents who report clinical PTSD symptoms are randomly allocated to either EMDR therapy or a waitlist usual care group. Parents who do not report clinical PTSD symptoms only receive care as usual. Six weeks later, a post-test of phase 2 is conducted for all participating dyads. Primary study outcomes are disrupted parenting behavior, sensitive parenting behavior, and parental PTSD symptoms. Secondary study outcomes include PTSD symptoms and behavioral and emotional problems of the child.

Discussion
This study will inform and enhance the clinical field by providing new insights regarding effective treatment combinations for traumatized parents and their young children after interparental violence.

Trial registration
Netherlands Trial Register (NTR) NL9179. Registered 7 January 2021
A novel Bayesian adaptive design incorporating both primary and secondary endpoints for randomized IIB chemoprevention study of women at increased risk for breast cancer
Authors: Gajewski Byron J. , Kimler Bruce F. , Koestler Devin C. , Mudaranthakam Dinesh Pal , Young Kate , Fabian Carol J. 
Published: December 2022

Abstract
Background
Our randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint.

Methods
In this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67).

Results
We present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint.

Discussion
Our approach balances trial speed and the need for information on the single, key secondary endpoint.
Cardio-pulmonary parasites of the European wildcat (Felis silvestris) in Germany
Authors: Bisterfeld Katrin , Raulf Marie-Kristin , Waindok Patrick , Springer Andrea , Lang Johannes , Lierz Michael , Siebert Ursula , Strube Christina 
Published: December 2022

Abstract
Background
In the last years, research on feline cardio-pulmonary parasites has considerably increased in Europe. Not only domestic cats (Felis catus), but also European wildcats (Felis silvestris) can serve as definitive hosts for these nematodes. The F. silvestris population in Germany has been growing rapidly within the last decades; therefore, the assessment of its cardio-pulmonary parasite status is of importance to unravel whether the wildcat population serves as a substantial reservoir for these nematodes and might pose a health threat to domestic cats.

Methods
As part of a nature conservation project for European wildcats in the German federal state Rhineland-Palatinate, lungs (n = 128) and hearts (n = 111) of 128 F. silvestris found dead were examined for cardio-pulmonary parasites. All isolated parasites were identified morphologically, and results were confirmed by molecular analysis of a total of 3–11 specimens of each worm species.

Results
A total of 70.3% (90/128) wildcats were positive for at least one lungworm species. Angiostrongylus chabaudi was most common (53.1% [68/128]), followed by Aelurostrongylus abstrusus (42.2% [54/128]), Troglostrongylus brevior (31.3% [40/128]) and Capillaria spp. (3.1% [4/128]). Of note, about two-thirds of the infected wildcats harboured coinfections. Infection intensities ranged from 1 to 167 nematodes per wildcat. Generalised linear models revealed a strong correlation between A. chabaudi and A. abstrusus infection, and prevalences were higher in adult than in younger wildcats, except for T. brevior. Moreover, the T. brevior prevalence varied significantly with nutritional status.

Conclusions
This study shows that feline cardio-pulmonary nematodes are common parasites in European wildcats in Germany but do not appear to have a serious impact on the overall health of the population. Due to presumed spillover events via prey, cardio-pulmonary nematodes may circulate between the wildcat population and domestic cats and might therefore pose a health risk to individual domestic cats.

Graphical abstract
Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis
Authors: Kuramoto Junko , Arai Eri , Fujimoto Mao , Tian Ying , Yamada Yuriko , Yotani Takuya , Makiuchi Satomi , Tsuda Noboru , Ojima Hidenori , Fukai Moto , Seki Yosuke , Kasama Kazunori , Funahashi Nobuaki , Udagawa Haruhide , Nammo Takao , Yasuda Kazuki , Taketomi Akinobu , Kanto Tatsuya , Kanai Yae 
Published: December 2022

Abstract
Background
In recent years, non-alcoholic steatohepatitis (NASH) has become the main cause of hepatocellular carcinoma (HCC). As a means of improving the treatment of NASH-related HCCs based on early detection, this study investigated the feasibility of carcinogenic risk estimation in patients with NASH.

Results
Normal liver tissue (NLT), non-cancerous liver tissue showing histological findings compatible with non-alcoholic fatty liver from patients without HCC (NAFL-O), non-cancerous liver tissue showing NASH from patients without HCC (NASH-O), non-cancerous liver tissue showing non-alcoholic fatty liver from patients with HCC (NAFL-W), non-cancerous liver tissue showing NASH from patients with HCC (NASH-W) and NASH-related HCC were analyzed. An initial cohort of 171 tissue samples and a validation cohort of 55 tissue samples were used. Genome-wide DNA methylation screening using the Infinium HumanMethylation450 BeadChip and DNA methylation quantification using high-performance liquid chromatography (HPLC) with a newly developed anion-exchange column were performed. Based on the Infinium assay, 4050 CpG sites showed alterations of DNA methylation in NASH-W samples relative to NLT samples. Such alterations at the precancerous NASH stage were inherited by or strengthened in HCC samples. Receiver operating characteristic curve analysis identified 415 CpG sites discriminating NASH-W from NLT samples with area under the curve values of more than 0.95. Among them, we focused on 21 CpG sites showing more than 85% specificity, even for discrimination of NASH-W from NASH-O samples. The DNA methylation status of these 21 CpG sites was able to predict the coincidence of HCC independently from histopathological findings such as ballooning and fibrosis stage. The methylation status of 5 candidate marker CpG sites was assessed using a HPLC-based system, and for 3 of them sufficient sensitivity and specificity were successfully validated in the validation cohort. By combining these 3 CpG sites including the ZC3H3 gene, NAFL-W and NASH-W samples from which HCCs had already arisen were confirmed to show carcinogenic risk with 95% sensitivity in the validation cohort.

Conclusions
After a further prospective validation study using a larger cohort, carcinogenic risk estimation in liver biopsy specimens of patients with NASH may become clinically applicable using this HPLC-based system for quantification of DNA methylation.