Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term outcomes from the phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma

Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months’ follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months’ follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.
Total hip arthroplasty using highly cross-linked polyethylene in patients aged 50 years and younger : minimum 15-year follow-up.

AIMS Highly cross-linked polyethylene (HXLPE) has greatly improved the durability of total hip arthroplasty (THA) in young patients because of its improved wear characteristics. Few studies have followed this population into the second decade, and therefore the purpose of this investigation was to evaluate the clinical outcome for THA patients 50 years of age and younger at a minimum of 15 years postoperatively. The second purpose was to evaluate the radiological findings secondary to wear or mechanical failure of the implant. METHODS Between October 1999 and December 2005, 105 THAs were performed in 95 patients (53 female, 42 male) aged 50 years and younger (mean 42 years (20 to 50)). There were 87 patients (96 hips) that were followed for a minimum of 15 years (mean 17.3 years (15 to 21)) for analysis. Posterior approach was used with cementless fixation with a median head size of 28 mm. HXLPE was the acetabular bearing for all hips. Radiographs were evaluated for polyethylene wear, radiolucent lines, and osteolysis. RESULTS Clinical outcomes showed significant improvement of mean Harris Hip Scores from 52.8 (SD 13.5) preoperatively to 94.8 (SD 7.6) postoperatively. One hip was revised for recurrent instability, and there were no infections. No hips were revised for mechanical loosening or osteolysis. Mean polyethylene linear wear was 0.04 mm/year and volumetric wear was 6.22 mm3/year, with no significant differences between head size or material. Osteolysis was not present in any of the hips. CONCLUSION The use of HXLPE in THA for patients aged 50 years and younger has performed exceptionally well without evidence of significant wear causing mechanical loosening or necessitating revision. The radiolucent lines of the acetabular component must be followed to determine the prognostic significance. This investigation represents the longest clinical follow-up of a large, consecutive cohort of patients aged 50 years or younger with THA using HXLPE. This long-term analysis found negligible polyethylene wear, no incidence of aseptic loosening, and excellent clinical outcomes at and beyond 15 years of follow-up. Cite this article: Bone Joint J 2021;103-B(7 Supple B):78-83.
Deep-time convergent evolution in animal communication presented by shared adaptations for coping with noise in lizards and other animals.

Convergence in communication appears rare compared with other forms of adaptation. This is puzzling, given communication is acutely dependent on the environment and expected to converge in form when animals communicate in similar habitats. We uncover deep-time convergence in territorial communication between two groups of tropical lizards separated by over 140 million years of evolution: the Southeast Asian Draco and Caribbean Anolis. These groups have repeatedly converged in multiple aspects of display along common environmental gradients. Robot playbacks to free-ranging lizards confirmed that the most prominent convergence in display is adaptive, as it improves signal detection. We then provide evidence from a sample of the literature to further show that convergent adaptation among highly divergent animal groups is almost certainly widespread in nature. Signal evolution is therefore curbed towards the same set of adaptive solutions, especially when animals are challenged with the problem of communicating effectively in noisy environments.
Three-Dimensional Measurements in Assessing the Results of Inferior Turbinate Surgery

Objectives: Acoustic rhinometry is widely used in evaluating patients with nasal congestion, but it only has a partial correlation with patient symptoms. The use and focus of cone beam computed tomography (CBCT) scans are mainly on the paranasal sinuses and less on the nasal cavities. Therefore, information acquired from CBCT scans is not used to its full extent. In our present study, we have studied patients with enlarged inferior turbinates. Our aim was to investigate and compare the use of 3D volumetric measurements and cross-sectional area measurements taken from CBCT scans to results obtained from acoustic rhinometry. Material and methods: In total, 25 patients with enlarged inferior turbinates were studied. CBCT scans were obtained preoperatively and at twelve months postoperatively. 3D volumetric and cross-sectional area measurements were compared to results from acoustic rhinometry, the visual analogue scale (VAS) and Glasgow Health Status Inventory (GHSI) questionnaires. Results: A statistically significant change in 3D volume and cross-sectional area was measured in the anterior part of the inferior turbinate and surrounding air space after inferior turbinate surgery. VAS and GHSI results had mild correlations with the 3D volume and cross-sectional area measurements of the anterior part of the inferior turbinate. Acoustic rhinometry correlated with the air space 3D volume measurements in the anterior part. Conclusions: Fully utilized CBCT scans provide more comprehensive and accurate information. Furthermore, 3D analysis of the inferior turbinates provides valuable information and more precise measurements compared to acoustic rhinometry.
A quantitative evaluation of a regional Positive Behavioural Support workforce development approach.

BACKGROUND Research suggests that providing staff with input in relation to Positive Behavioural Support (PBS) can have beneficial outcomes. Much of this research, however, fails to take account of systemic issues and does not include a control group. METHOD We used a non-randomised, controlled group design to evaluate accredited PBS programmes, delivered as part of a systemic, regional and workforce development approach. We compared outcomes of those attending the programmes (n = 240) with a control group (n = 54), pre- and post-intervention and at 3-months follow-up. RESULTS The programme and its wider impact were rated positively. Significant intervention effects were found for staff practice and retention, but not for staff knowledge and attributions, or behaviours that challenge and quality of life of those being supported. CONCLUSIONS The results are discussed in the context of the study limitations and restrictions resulting from the Covid-19 pandemic.
Three-dimensional superresolution fluorescence microscopy maps the variable molecular architecture of the nuclear pore complex

Nuclear pore complexes (NPCs) are large macromolecular machines that mediate the traffic between the nucleus and the cytoplasm. In vertebrates, each NPC consists of ∼1000 proteins, termed nucleoporins, and has a mass of more than 100 MDa. While a pseudo-atomic static model of the central scaffold of the NPC has recently been assembled by integrating data from isolated proteins and complexes, many structural components still remain elusive due to the enormous size and flexibility of the NPC. Here, we explored the power of three-dimensional (3D) superresolution microscopy combined with computational classification and averaging to explore the 3D structure of the NPC in single human cells. We show that this approach can build the first integrated 3D structural map containing both central as well as peripheral NPC subunits with molecular specificity and nanoscale resolution. Our unbiased classification of more than 10,000 individual NPCs indicates that the nuclear ring and the nuclear basket can adopt different conformations. Our approach opens up the exciting possibility to relate different structural states of the NPC to function in situ.
Recurrence and new tumor development after frontline intravenous chemotherapy for retinoblastoma: Risk factors and treatment results

Purpose: To evaluate the risk factors leading to recurrence and new tumor (NT) development in patients with retinoblastoma after intravenous chemotherapy (IVC) and to review the treatment outcomes. Materials and methods: The records of 166 retinoblastoma cases (having 246 affected eyes) who underwent six-cycle IVC (vincristine, etoposide, and carboplatin) as primary treatment between October 1999 and August 2020 were reviewed retrospectively. Results: The mean ages at presentation were 9.0 (median: 8.0) and 9.2 (median: 8.5) months in cases with recurrence and NTs respectively. Recurrence was detected in 40 (16.3%) eyes, NTs in 29 (11.8%), and both recurrence/NTs in 24 (9.8%). The mean time elapsed till recurrence and NT was 10.7 months. Multivariable analysis showed that the factors predictive of recurrence were largest tumor base diameter (LTBD) >12 mm (p = 0.039) and presence of subretinal seeds at diagnosis (p = 0.043). Multivariable risk factors for the development of NTs were bilateral familial retinoblastoma (p = 0.001) and presence of subretinal seeds at diagnosis (p = 0.010). Mean follow-up was 80.1 (median: 72.5) months. By Kaplan-Meier analysis, the 1-, 3-, and 6-year recurrence and NT rates were 21.2%, 28.1%, and 28.7% and 14.9%, 22.6%, and 23.9% respectively. The most common treatment methods used for recurrent and/or NTs included cryotherapy, transpupillary thermotherapy, and intra-arterial chemotherapy. Enucleation was eventually required in 24/93 (25.8%) eyes. No patient developed metastasis. Discussion: Development of recurrence and/or NT after IVC was noted in 38% of all retinoblastoma eyes. Bilateral familial disease, LTBD >12 mm, and presence of subretinal seeds at baseline were risk factors for recurrence and NTs in this study.
A tale of two cultural life scripts: do young second-generation Turkish immigrants versus young Danes in Denmark perceive life through different cultural lenses?

ABSTRACT Cultural life scripts refer to the shared expectations as to the order and timing of life events in a prototypical life course within a given culture or subculture. Immigration is a significant transition that often implies a change in cultural context, which may change people's views about a normative life. However, research on cultural life scripts in the context of immigration has been limited. We addressed this gap by examining the cultural life scripts of 33 young second-generation Turkish immigrants and 33 young Danes in Denmark, pairwise-matched on age, gender, and education, along with their subjective well-being and acculturation level. Both groups reported mostly positive life script events expected to occur in early adulthood and their individual life scripts generally had a positive outlook. In contrast to earlier studies, we found no evidence of lower subjective well-being or greater normativity of the cultural life script in the immigrant group. Moreover, the acculturation level of the Turkish group correlated positively with their subjective well-being, suggesting that adapting at least to some degree to the daily life of the host country is associated with well-being of second-generation immigrants.
Plague Exposure in Mammalian Wildlife Across the Western United States

Plague is caused by a bacterial pathogen (Yersinia pestis) that can infect a wide range of mammal species, but its presence in wildlife is often underappreciated. Using a large-scale data set (n = 44,857) that details the extent of Y. pestis exposure in wildlife, we document exposure in 18 wildlife species, including coyotes (Canis latrans), bobcats (Lynx rufus), and black bears (Ursus americanus). Evidence of plague activity is widespread, with seropositive animals detected in every western state in the contiguous United States. Pathogen monitoring systems in wildlife that are both large scale and long-term are rare, yet they open the door for analyses on potential shifts in distribution that have occurred over time because of climate or land use changes. The data generated by these long-term monitoring programs, combined with recent advances in our understanding of pathogen ecology, offer a clearer picture of zoonotic pathogens and the risks they pose.
Extreme insulin resistance during pregnancy: a therapeutic challenge

Summary During pregnancy, maternal tissues become increasingly insensitive to insulin in order to liberate nutritional supply to the growing fetus, but occasionally insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme insulin resistance with daily insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a hemoglobin A1c (HbA1c) at 59 mmol/mol. Insulin treatment was initiated immediately using Novomix 30, and the doses were progressively increased, peaking at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in insulin requirements, but with no signs of placental insufficiency. At week 36 + 1 a, healthy baby with no hypoglycemia was delivered by cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme insulin resistance and showed high levels of C-peptide, proinsulin, insulin-like growth factor (IGF-1), mannan-binding-lectin (MBL) and leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal. Insulin antibodies were undetectable, and no mutations in the insulin receptor (INSR) gene were found. The explanation for the severe insulin resistance, in this case, can be ascribed to PCOS, obesity, profound weight gain, hyperleptinemia and inactivity. This is the first case of extreme insulin resistance during pregnancy, with insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists. Learning points This is the first case of extreme insulin resistance during pregnancy, with insulin requirements of up to 1420 IU/day with a successful outcome without significant fetal macrosomia and hypoglycemia. Obesity, PCOS, T2D and high levels of leptin and IGF-1 are predictors of severe insulin resistance in pregnancy. A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.
ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2-Evidence Base and Standardized Methods of Imaging.

remission/progression complementing clinical evaluation. Additional areas not deﬁned include appropriate clinical indications for imaging, optimal imaging utilization by clinical presentation, accepted imaging methods, accurate image interpretation, and comprehensive and clear reporting. Prospective randomized clinical trial data for the diagnosis of amyloidosis and for imaging-based strategies for treatment are not available. A consensus of expert opinion is greatly needed to guide the appropriate clinical utilization of imaging in cardiac amyloidosis
Microencapsulation: a pragmatic approach towards delivery of probiotics in gut

Abstract Probiotics confer numerous health benefits and functional foods prepared with these microbes own largest markets. However, their viability during transit from gastrointestinal tract is a concerning issue. Microencapsulation of probiotics is a novel technique of major interest to increase their survivability in GIT and food matrices by providing a physical barrier to protect them under harsh conditions. This article contributes the knowledge regarding microencapsulation by discussing probiotic foods, different methods and approaches of microencapsulation, coating materials, their release mechanisms at the target site, and interaction with probiotics, efficiency of encapsulated probiotics, their viability assessment methods, applications in food industry, and their future perspective. In our opinion, encapsulation has significantly got importance in the field of innovative probiotic enriched functional foods development to preserve their viability and long-term survival rate until product expiration date and their passage through gastro-intestinal tract. Previous review work has targeted some aspects of microencapsulation, this article highlights different methods of probiotics encapsulation and coating materials in relation with food matrices as well as challenges faced during applications: Gut microbiota; Lactic acid bacteria; Micro-encapsulation; Stability enhancement; Cell’s release, Health benefits.
Chronic, Episodic Nicotine Alters Hypoglossal Motor Neuron Function at a Critical Developmental Time Point in Neonatal Rats

Abstract Developmental nicotine exposure (DNE), alters brainstem neurons that control breathing, including hypoglossal motor neurons (XIIMNs), which innervate the tongue. Here, we tested the hypothesis that chronic, episodic DNE (eDNE), which mimics nicotine replacement therapies such as e-cigarettes or nicotine gum, alters the function of nicotinic acetylcholine receptors (nAChRs), XIIMN intrinsic properties, and tongue muscle function in vivo similar to what we have observed with a chronic, sustained exposure model. We delivered nicotine to pregnant Sprague Dawley rats through drinking water and studied pups of either sex in two age groups: postnatal day (P)1–P5 and P10–P12, which encompasses a critical period in brain development. At P1–P5, eDNE was associated with delayed recovery of nAChRs from desensitization; however, there were no changes in the magnitude of desensitization, XIIMN intrinsic properties, or tongue muscle function in vivo. By P10–P12, eDNE XIIMNs had lower peak firing frequencies in response to depolarizing current injection, larger delayed rectifier potassium currents, and continued to exhibit delayed nAChR recovery. Moreover, this age group exhibited a blunted and delayed tongue muscle response to nasal occlusion in vivo, indicating that changes to XIIMN intrinsic properties is an important mechanism behind this effect, as it is not produced by altered nAChR function alone. Together, these results show that eDNE alters XIIMNs and tongue muscle function during a critical period in brain development and that the specific effects of chronic nicotine exposure may be pattern dependent.
Mental health and social support among nurses during the COVID-19 pandemic

ABSTRACT This study aimed to investigate the prevalence of mental problems and social support among nurses during the COVID-19 epidemic and to explore the correlation. We carried out a multicentre, large-sample questionnaire survey in Chongqing (China). The WeChat-based survey program Questionnaire Star was used to distribute a questionnaire with self-designed items to obtain general information, the Depression, Anxiety and Stress Scale-21 (DASS-21), and the Social Support Rating Scale (SSRS). A total of 848 neonatal nurses participated. The results showed that 104 nurses (12.3%) had depression symptoms, 133 (15.7%) had anxiety symptoms, and 45 (5.3%) had stress symptoms. However, the DASS-21 score of the majority of nurses was normal. Pearson correlation analyses revealed that mental health was negatively correlated with social support, indicating that the higher social support was, the better the psychological condition of nurses.
Interstitial amyloidosis in sporadic inclusion body myositis

Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis.
The quantification of liver fat from wave speed and attenuation

A framework is developed for estimating the volume fraction of fat in steatotic livers from viscoelastic measures of shear wave speed and attenuation. These measures are emerging on clinical ultrasound systems’ elastography options so this approach can become widely available for assessing and monitoring steatosis. The framework assumes a distribution of fat vesicles as spherical inhomogeneities within the liver and uses a composite rheological model (Christensen 1969 J. Mech. Phys. Solids 17 23–41) to determine the shear modulus as a function of increasing volume of fat within the liver. We show that accurate measurements of shear wave speed and attenuation provide the necessary and sufficient information to solve for the unknown fat volume and the underlying liver stiffness. Extension of the framework to compression wave measurements is also possible. Data from viscoelastic phantoms, human liver studies, and steatotic animal livers are shown to provide reasonable estimates of the volume fraction of fat.