Miracle-dz/UniFAR-FTUs huggingface dataset:
Opportunistic Screening With CT: Comparison of Phantomless BMD Calibration Methods

Opportunistic screening is a new promising technique to identify individuals at high risk for osteoporotic fracture using computed tomography (CT) scans originally acquired for an clinical purpose unrelated to osteoporosis. In these CT scans, a calibration phantom traditionally required to convert measured CT values to bone mineral density (BMD) is missing. As an alternative, phantomless calibration has been developed. This study aimed to review the principles of four existing phantomless calibration methods and to compare their performance against the gold standard of simultaneous calibration (ΔBMD). All methods were applied to a dataset of 350 females scanned with a highly standardized CT protocol (DS1) and to a second dataset of 114 patients (38 female) from clinical routine covering a large range of CT acquisition and reconstruction parameters (DS2). Three of the phantomless calibration methods must be precalibrated with a reference dataset containing a calibration phantom. Sixty scans from DS1 and 57 from DS2 were randomly selected for this precalibration. For each phantomless calibration method first the best combination of internal reference materials (IMs) was selected. These were either air and blood or subcutaneous adipose tissue, blood, and cortical bone. In addition, for phantomless calibration a fifth method based on average calibration parameters derived from the reference dataset was applied. For DS1, ΔBMD results (mean ± standard deviation) for the phantomless calibration methods requiring a precalibration ranged from 0.1 ± 2.7 mg/cm3 to 2.4 ± 3.5 mg/cm3 with similar means but significantly higher standard deviations for DS2. Performance of the phantomless calibration method, which does not require a precalibration was worse (ΔBMD DS1: 12.6 ± 13.2 mg/cm3, DS2: 0.5 ± 8.8 mg/cm3). In conclusion, phantomless BMD calibration performs well if precalibrated with a reference dataset. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Improved diagnosis of reflux hypersensitivity

Reflux hypersensitivity (RH) is characterized by normal esophageal exposure to acid and positive correlation of symptoms to reflux episodes. Positivity of Symptomatic Index (SI) and/or Symptom Association Probability (SAP) is used diagnostically, though experts support that concordance of both is needed. We evaluated differences among patients with RH and concordance of SI/SAP or not.
Health‐related quality of life and mild behavioral impairment in older adults without dementia

The Mild Behavioral Impairment Checklist (MBI‐C) was developed to assess neuropsychiatric symptoms (NPS) and to identify mild behavioral impairment (MBI). This study validated the Taiwanese version of the MBI‐C and examined its association of health‐related quality of life (HR‐QoL).
“It depends on the boss” – a qualitative study of multi-level interventions aiming at office workers’ movement behaviour and mental health

ABSTRACT Purpose This embedded qualitative study explored the acceptability, feasibility, and fidelity of two multi-level RCT interventions among office workers, aiming at improving movement behaviour to enhance mental health and cognition. The interventions addressed the organizational, environmental, and individual level. Methods Semi-structured interviews and focus group discussions were conducted with 38 stakeholders after completion of the interventions. Data were analysed using reflexive thematic analysis. Results The interventions were well appreciated, and office workers attributed improvements in movement behaviour and wellbeing to the interventions. Especially the cognitive behavioural therapy (CBT) based counselling and free gym access were appreciated, feasible and delivered as planned. Participants described existing workplace norms as barriers to more activity, particularly for reducing sitting. Support from managers and team support were considered crucial components. However, delivering these components was difficult. Conclusions The findings support the design of the multi-level interventions for changing movement behaviour. Results highlight the potential of CBT for this target group and the importance of manager and team support. Desired effects of similar multi-level interventions, including CBT, might be achieved in future studies that carefully address the issues with feasibility and acceptability and the resulting low fidelity of some intervention components that were identified in this study.
Effects of Social Support, Family Resilience, and Individual Resilience on Fear of Cancer Recurrence Among Persons With Breast Cancer: A Cross-Sectional Study

Background: There is limited research exploring the psychological and social predictors of fear of cancer recurrence (FCR). Objective: This study tested the effects of social support, family resilience, and individual resilience on FCR among persons with breast cancer. Methods: A convenience sampling method was used to select 214 participants from March to August 2021 in 1 tertiary hospital in Jinan, China. Data were collected using self-administered questionnaires. Path analysis was adopted to explore the effects of social support, family resilience, and individual resilience on FCR. Results: Findings showed that 94.6% of the participants reached a clinical level of FCR. Social support (β = −.75, p < .01) and individual resilience (β = −.32, p < .01) negatively and directly impacted FCR. Family resilience indirectly impacted FCR through individual resilience (β = −.22, 95% confidence interval (CI): −. 34 to −. 08). Social support indirectly impacted FCR through family resilience and individual resilience (β = −.15, 95% CI: −.23 to −.06). Conclusions: Persons with breast cancer experienced a high level of FCR. Individual resilience was a mediator between family resilience and FCR. Resilience (individual resilience and family resilience) partially mediated the effects of social support on FCR. The findings indicate that measures focused on improving individual resilience, family resilience, and social support should be considered by nurses, which are helpful for easing FCR.
Belgian Culex pipiens pipiens are competent vectors for West Nile virus while Culex modestus are competent vectors for Usutu virus

Background West Nile virus (WNV) and Usutu virus (USUV) are emerging arthropod-borne viruses (arboviruses) in Europe transmitted by Culex mosquitoes. In Belgium, it is currently unknown which Culex species are competent vectors for WNV or USUV and if these mosquitoes carry Wolbachia, an endosymbiotic bacterium that can block arbovirus transmission. The aims of our study were to measure the vector competence of Belgian Culex mosquitoes to WNV and USUV and determine if a naturally acquired Wolbachia infection can influence virus transmission. Methodology/Principal findings Female Culex mosquitoes were captured from urban and peri-urban sites in Leuven, Belgium and offered an infectious bloodmeal containing WNV lineage 2, USUV European (EU) lineage 3, or USUV African (AF) lineage 3. Blood-fed females were incubated for 14 days at 25°C after which the body, head, and saliva were collected to measure infection, dissemination, and transmission rates as well as transmission efficiency. Mosquito species were identified by qRT-PCR or Sanger sequencing, the presence of infectious virus in mosquitoes was confirmed by plaque assays, and viral genome copies were quantified by qRT-PCR. Culex pipiens pipiens were able to transmit WNV (4.3% transmission efficiency, n = 2/47) but not USUV (EU lineage: n = 0/56; AF lineage: n = 0/37). In contrast, Culex modestus were able to transmit USUV (AF lineage: 20% transmission efficiency, n = 1/5) but not WNV (n = 0/6). We found that the presence or absence of Wolbachia was species-dependent and did not associate with virus transmission. Conclusions/Significance This is the first report that Belgian Culex mosquitoes can transmit both WNV and USUV, forewarning the risk of human transmission. More research is needed to understand the potential influence of Wolbachia on arbovirus transmission in Culex modestus mosquitoes.
Suitability of respiratory endoscopy for sampling malignant thoracic tumors for comprehensive genomic profiling

Comprehensive genomic profiling (CGP) is implemented to detect actionable gene aberrations and design matched therapies. Although malignant thoracic tumors are commonly detected through respiratory endoscopy, it is questionable whether the small specimens obtained thereof are sufficient for CGP. Therefore, this study aimed to investigate the suitability of respiratory endoscopy for sampling primary and metastatic thoracic tumors for CGP. Patients whose specimens were collected through respiratory endoscopy and assessed by pathologists to determine their suitability for CGP at our institution between June 2019 and May 2022 were reviewed retrospectively. The suitability of each procedure as a sampling technique for CGP and, in the cases actually analyzed, the distribution of the detected gene aberration were assessed. In total, 122 patients were eligible for analysis; the median age was 61 (range, 29–86) years, and 71 (58.2%) patients were male. Primary intrathoracic tumors were found in 91 (74.6%) cases, including 84 (68.9%) primary lung cancers; the remaining thoracic metastases of extrathoracic origin included various types. The suitability rates of specimens obtained using conventional bronchoscopy with and without cryobiopsy, endobronchial ultrasound‐guided transbronchial needle aspiration, and medical thoracoscopy were 82.8% (24/29), 70.4% (19/27), 72.9% (35/48), and 100% (18/18), respectively. Of the 96 cases judged suitable, 83 were subjected to CGP, and all but one were successfully analyzed. Finally, 47 (56.6%) patients had at least one actionable gene aberration and eight (9.6%) were treated with the corresponding targeted therapies. In conclusion, specimens obtained through respiratory endoscopy are suitable for CGP; medical thoracoscopy and cryobiopsy in conventional bronchoscopy are particularly useful.
Interruption of BTK inhibitor improves response to SARS-CoV-2 booster vaccination in patients with CLL

Abstract B-cell targeted therapies, including anti-CD20 monoclonal antibodies (mAb) and Bruton’s tyrosine kinase inhibitors (BTKi), further suppress antibody (Ab) response to vaccines in patients with chronic lymphocytic leukemia (CLL). We conducted a prospective cohort study of SARS-CoV-2 vaccination in 81 CLL patients receiving BTKi (n = 54), venetoclax (VEN, n = 9), or who were treatment naïve (TN, n = 18). Anti-spike Ab were detected in 53% of patients on BTKi post-primary series and 84% post-booster, 57% of patients on VEN post-primary series and 50% post-booster, and 67% of TN patients post-primary series and 87% post-booster. T-cell response to the primary series was independent of Ab response. At the time of booster, 12 patients interrupted BTKi (median 21 d, range 8–22) and 33 continued BTKi. Among patients with detectable Ab post-booster, those who interrupted BTKi (n = 10) had significantly higher Ab titers (median 7149 units/mL) compared with patients who continued BTKi (n = 27, median 2071 units/mL, p = .04).
In vitro fertilization program in white rhinoceros

In brief To save endangered rhinoceros species, assisted reproductive technologies are warranted. We here report in vitro blastocyst generation of the Near-Threatened Southern white rhinoceros and, for the first time, also of the technically Extinct Northern white rhinoceros. Abstract The Anthropocene is marked by a dramatic biodiversity decline, particularly affecting the family Rhinocerotidae. Three of five extant species are listed as Critically Endangered (Sumatran, Javan, black rhinoceros), one as Vulnerable (Indian rhinoceros), and only one white rhino (WR) subspecies, the Southern white rhinoceros (SWR), after more than a century of successful protection is currently classified as Near Threatened by the IUCN, while numbers again are declining. Conversely, in 2008, the SWR’s northern counterpart and second WR subspecies, the Northern white rhinoceros (NWR), was declared extinct in the wild. Safeguarding these vanishing keystone species urgently requires new reproductive strategies. We here assess one such strategy, the novel in vitro fertilization program in SWR and – for the first-time NWR – regarding health effects, donor-related, and procedural factors. Over the past 8 years, we performed 65 procedures in 22 white rhinoceros females (20 SWR and 2 NWR) comprising hormonal ovarian stimulation, ovum pick-up (OPU), in vitro oocyte maturation, fertilization, embryo culture, and blastocyst cryopreservation, at an efficiency of 1.0 ± 1.3 blastocysts per OPU, generating 22 NWR, 19 SWR and 10 SWR/NWR hybrid blastocysts for the future generation of live offspring.
PNPLA6 disorders: what’s in a name?

ABSTRACT Background Variants in the patatin-like phospholipase domain containing 6 (PNPLA6) gene cause a broad spectrum of neurological disorders characterized by gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. This review examines the clinical, cellular, and biochemical features found across the five PNPLA6-related diseases, with a focus on future questions to be addressed. Materials and Methods A literature review was performed on published clinical reports on patients with PNPLA6 variants. Additionally, in vitro and in vivo models used to study the encoded protein, Neuropathy Target Esterase (NTE), are summarized to lend mechanistic perspective to human diseases. Results Biallelic pathogenic PNPLA6 variants cause five systemic neurological disorders: spastic paraplegia type 39, Gordon-Holmes, Boucher-Neuhäuser, Laurence-Moon, and Oliver-McFarlane syndromes. PNPLA6 encodes NTE, an enzyme involved in maintaining phospholipid homeostasis and trafficking in the nervous system. Retinal disease presents with a unique chorioretinal dystrophy that is phenotypically similar to choroideremia and Leber congenital amaurosis. Animal and cellular models support a loss-of-function mechanism. Conclusions Clinicians should be aware of choroideremia-like ocular presentation in patients who also experience growth defects, motor dysfunction, and/or hair anomalies. Although NTE biochemistry is well characterized, further research on the relationship between genotype and the presence or absence of retinopathy should be explored to improve diagnosis and prognosis.
Dynamic top-down biasing implements rapid adaptive changes to individual movements

Complex behaviors depend on the coordinated activity of neural ensembles in interconnected brain areas. The behavioral function of such coordination, often measured as co-fluctuations in neural activity across areas, is poorly understood. One hypothesis is that rapidly varying co-fluctuations may be a signature of moment-by-moment task-relevant influences of one area on another. We tested this possibility for error-corrective adaptation of birdsong, a form of motor learning which has been hypothesized to depend on the top-down influence of a higher-order area, LMAN (lateral magnocellular nucleus of the anterior nidopallium), in shaping moment-by-moment output from a primary motor area, RA (robust nucleus of the arcopallium). In paired recordings of LMAN and RA in singing birds, we discovered a neural signature of a top-down influence of LMAN on RA, quantified as an LMAN-leading co-fluctuation in activity between these areas. During learning, this co-fluctuation strengthened in a premotor temporal window linked to the specific movement, sequential context, and acoustic modification associated with learning. Moreover, transient perturbation of LMAN activity specifically within this premotor window caused rapid occlusion of pitch modifications, consistent with LMAN conveying a temporally localized motor-biasing signal. Combined, our results reveal a dynamic top-down influence of LMAN on RA that varies on the rapid timescale of individual movements and is flexibly linked to contexts associated with learning. This finding indicates that inter-area co-fluctuations can be a signature of dynamic top-down influences that support complex behavior and its adaptation.
Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice

ABSTRACT Zika virus (ZIKV) infection in pregnant women during the first trimester can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen. By contrast, ZIKV infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in newborns without microcephaly. Here, we evaluated the long-term fertility consequences of ZIKV infection in male suckling mice, which is equivalent to congenital ZIKV infection in children, from multiple perspectives including the hypothalamic-pituitary-gonadal axis, testis, sperm, and social behaviors. We observed the persistence of ZIKV in the hypothalamus of mice, which caused long-term hormone deficiencies of the hypothalamic-pituitary-gonadal axis. Hormone deficiencies led to limited delays in testicular development, a decrease in sperm quality and quantity, and abnormal social abilities. These damages could progress to diminished fertility in male mice, as judged by lower pregnancy rate, prolonged time to delivery, and decreased offspring quality. Currently, the extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of hormone levels and reproductive health in ZIKV-exposed children seem warranted. IMPORTANCE Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality. Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality.
Prediction of cytology–histology discrepancy when Bethesda cytology reports benign results for thyroid nodules in women: with special emphasis on pregnancy

ABSTRACT Objectives: Benign category of Bethesda classification is generally well known to carry a false-negative rate of 0–3%. The current study was designed to investigate the rate of false-negative cytology in patients who underwent thyroidectomy for presumably benign thyroid diseases. Predictive risk factors for false results and malignancy were evaluated along with cytology–histology discrepant cases. Materials and methods: Females who underwent thyroidectomy between May 2014 and December 2022 were included. Demographics, ultrasound (US) features, fine-needle aspiration (FNA) diagnosis, surgical indications and outcomes, final histology reports, risk factors, and malignancy rate were recorded. Cytology–histology discrepant cases were further evaluated for interpretation errors and risk factors. Statistical analyses were performed using Fisher’s exact and Mann–Whitney U tests. Results: Of 581 women with a benign thyroid disease who underwent thyroidectomy, 91 was diagnosed as incidental carcinoma (15.6%) and most was T1a (4.9 ± 2.7 mm, 95.6%). Final histology reports revealed mostly papillary carcinoma (93.4%). Predictors of malignancy such as age, family history, previous radiation exposure, and iodine-deficient diet did not help in risk stratification (p > 0.05, for each). However, FNA taken during pregnancy was determined as a risk factor (n = 7, 7.6%, p < 0.05) since it may cause a delay in diagnosis. Cytology–histology discrepant cases were seen to be mostly due to sampling errors (45%, p < 0.05), followed by misinterpretations (37.3%, p < 0.05). There was no reason for discrepancy in 17.5%, and this was linked to inherent nature of thyroid nodule with overlapping cytologic features. Best identifiable risk factor for misinterpretation was pregnancy as well (n = 5, 14.7%, p < 0.05). Conclusions: Risk of malignancy in a presumably benign thyroid disease should not be ignored. Radiology–cytology correlation by an experienced dedicated team may help in decreasing sampling errors. Physiologic changes caused by pregnancy may shade malignant transformation in thyrocytes, and it would be appropriate to be cautious about benign FNA taken during this period.
Real-world adherence and discontinuation among Medicare beneficiaries initiating venetoclax vs. BTKis in relapsed/refractory chronic lymphocytic leukemia

Abstract The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton’s tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015–2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12 months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p < .001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p < .001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults.