Miracle-dz/UniFAR-FTUs huggingface dataset:
Beneficial effects of modulated electro-hyperthermia during neoadjuvant treatment for locally advanced rectal cancer

Abstract Purpose Modulated electro-hyperthermia (mEHT) may enhance the tumor response, although the effectiveness of combined neoadjuvant therapy remains unclear. Therefore, we investigated the role of mEHT with neoadjuvant therapy for locally advanced rectal cancer. Materials and methods Clinical data were analyzed for 120 patients who received neoadjuvant treatment for locally advanced rectal cancer (T3/4 or N+, M0) from May 2012 to December 2017. Capecitabine or 5-fluorouracil was administered along with radiotherapy. Patients were categorized into mEHT group (62 patients) and non-mEHT group (58 patients) depending on whether mEHT was added. Surgery was performed 6–8 weeks after the end of radiotherapy. Results The median age was 59 years (range, 33–83). The median radiation dose was significantly less for mEHT group (40 Gy) than for non-mEHT group (50.4 Gy). In mEHT group, 80.7% showed down-staging compared with 67.2% in non-mEHT group. For large tumors of more than 65 cm³ (mean), improved tumor regression was observed in 31.6% of mEHT group compared with 0% of non-mEHT group (p = .024). The gastrointestinal toxicity rate of mEHT group was 64.5%, which was found to be statistically significantly less than 87.9% of non-mEHT group (p = .010). The 2-year disease-free survival was 96% for mEHT group and 79% for non-mEHT group (p = .054). Conclusion The overall mEHT group had a comparable response and survival using less radiation dosing compared with standard care; the subgroup with large tumors showed improved efficacy for tumor regression after mEHT.
The Use of Biphasic Calcium Phosphate Substitute (BCP) in Mandibular Defects in Dogs: Use of CBCT to Evaluate Bone Healing

This study aimed to assess the use of cone beam computed tomography (CBCT) to follow-up bone healing of mandibular bone defects in dogs, filled with a combination of autologous blood and millimetric BCP granules. CBCT was performed ≥4 weeks postoperatively. CBCT gray-scale values were measured from multiplanar reconstructions of the defects and compared to that of normal contralateral mandibular bone and to pure BCP/blood composite time 0 (T0) value. Other parameters, determined by affecting grades according to specific criteria included: bone ridge margin restoration; biomaterial homogeneity; bone-biomaterial interface. Results: 8 dogs with 14 defects were included. Median age was 7.2 years (1-15 years). Follow-up CBCT was performed 1 to 7.5 months postoperatively (mean 3.3 months). Defect CBCT gray-scale values at follow-up were significantly greater than T0 (p < 0.05). Ratios of maximum and minimum densities of the defects to contralateral mandibular bone followed a linear correlation with time (p < 0.05). The bone ridge margin was adequately restored in all the defects and significantly correlated with time (p = 0.03). Biomaterial homogeneity was fair to good in 11 defects and significantly correlated with the bone ridge margin parameter (p = 0.05) and time (p = 0.006). There was no significant correlation with the bone-material interface. The latter was satisfactory in 12 defects and significantly correlated with time (p = 0.01) but not with the other parameters. The biomaterial was more homogeneous in smaller defects and with increasing time. CBCT allowed effective assessment of bone healing via the measurement of CBCT gray-scale values and assessment of multiple radiological variables.
Cord-Blood High-Sensitivity Troponin-I Reference Interval and Association with Early Neonatal Outcomes

Abstract Objective This study was aimed to establish a reference interval for high-sensitivity cardiac troponin I (hs-cTnI) in umbilical cord blood of infants and to assess its association with the risk of predetermined early neonatal outcomes in a high-acuity tertiary care hospital. Study Design Umbilical cord-blood samples were collected and hs-cTnI was measured in all infants born between August 2015 and September 2015 at McMaster Children's Hospital (n = 256). Gestational age, birth weight, Apgar's scores, age in days at which feeding was established, neonatal intensive care unit (NICU) admission, and discharge in days after birth were recorded. Results The 90th, 95th, and 99th percentiles for the term infant subcohort were 19.75, 41.45, and 166.30 ng/L, respectively. We observed decreased mean gestational ages and birth weights in both the 90th (37.7 weeks; 2,961.4 g) and 95th percentiles (37.1 weeks; 2,709.9 g) when compared with the remaining infants. Moreover, levels of hs-cTnI were significantly higher in infants with respiratory distress requiring intervention (p < 0.05), low–birth weight infants (p < 0.01), preterm infants (p < 0.001), and those requiring NICU admission (p < 0.01). Multiple linear regression of the recorded demographic factors revealed prematurity (gestational age <35 weeks: coefficient 0.346 ± 0.160, p < 0.05; gestational age <37 weeks: coefficient 0.253 ± 0.105, p < 0.05) and male sex (coefficient 0.138 ± 0.047; p < 0.01) to be most predictive of log-hs-cTnI levels. Conclusion This study establishes the reference values for cord-blood hs-cTnI in infants at a tertiary care center. Premature and sick infants requiring NICU admission had significantly higher levels of hs-cTnI. Key Points Established the 90th, 95th, and 99th percentiles of neonatal cord-blood hs-cTnI in term infants as 19.75, 41.45, and 166.30 ng/L, respectively. Infants with hs-cTnI levels exceeding the 90th percentile had lower gestational ages and birth weights with higher rates of NICU admissions. Infants with respiratory distress or requiring NICU admission were found to have higher levels of hs-cTnI.
Competition Volume and Changes in Countermovement Jump Biomechanics and Motor Signatures in Female Collegiate Volleyball Players.

ABSTRACT Kipp, K, Kiely, M, and Geiser, C. Competition volume and changes in countermovement jump biomechanics and motor signatures in female collegiate volleyball players. J Strength Cond Res XX(X): 000-000, 2020-The purpose of this study was to investigate the relationship between competition volume and preseason to postseason changes in countermovement jump (CMJ) biomechanics and motor signatures in female collegiate volleyball players. Ten National Collegiate Athletic Association Division I female volleyball players performed CMJs on force plates before (PRE) and after (POST) their season. Countermovement jump height was calculated, and 4 discrete biomechanical variables (peak body-mass normalized force [PeakF], peak body-mass normalized rate of force development [PeakRFD], movement time [TIME], and the ratio between eccentric and total movement time [EccT:TIME]) were calculated. A factor analysis of the 4 biomechanical variables was used to identify CMJ motor signatures. The total number of sets played by each player was used to define total competition volume for the season. Correlation coefficients were used to investigate the associations between competition volume and changes in CMJ height, discrete biomechanical variables, and the components of the CMJ motor signature. The statistical analysis indicated that team-average jump height did not change over the course of the season. However, competition volume was negatively associated with changes in CMJ height, such that decreases in CMJ height over the course of the season occurred in players who played large numbers of sets. Although CMJ during POST testing was characterized by longer TIME and greater PeakRFD, CMJ motor signatures did not change and suggest that the female volleyball players in this study retained their preferred jumping strategy across the season. Given that decreases in CMJ height were most pronounced in players who played the most sets, and scored the most points during the season, future research may need to focus on player- or position-specific interventions that help players retain CMJ performance in the face of the competitive demands of a collegiate volleyball season.
Family readiness for evidence-based injury prevention and car seat safety in Jordan

Abstract Primary prevention involves developing positive health behaviours designed to avert adverse health outcomes, whereas evidence-based primary prevention adopts practices that reduce illness and injury. This study’s objective was to determine whether families in Jordan would adopt car safety measures after participating in an evidence-based injury prevention programme. Parents of children attending a regional government hospital in Jordan took part in an evidence-based educational class on child car restraints and car safety, six months later follow-up phone calls were made to see if the parents implemented the knowledge obtained in the class. Fifty families participated in the injury prevention class. The results showed that the evidence-based class on child restraint systems led to the adoption of the three interventions by the parents. At the time of the class 45% of parents allowed their infants to sit in the front seat, in the lap of an adult, this was reduced to 12%, being a 33% reduction. In addition, for children aged 6–12 using a seat belt in the back seat, the parents reported that their children using a seat belt increased from 13% to 70%. Finally, parents who participated were more likely to use a child car seat.
Impact of Tumor Site and Adjuvant Radiotherapy on Survival of Patients with Adenoid Cystic Carcinoma: A SEER Database Analysis

Simple Summary Adenoid cystic carcinoma (ACC) is a rare but lethal salivary gland tumor, comprising less than 1% of head and neck neoplasms. It can affect several sites in the head and neck region, but the potential role of tumor site on survival and treatment response remains unclear and, to this day, the role that tumor location plays in treatment planning and survival has not been considered. We sought to address these knowledge gaps via analyses of the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis identified that patients with submandibular gland adenoid cystic carcinomas, particularly those with late-stage disease, had worse survival compared to other sites and benefited the most from adjuvant radiotherapy. In contrast, early-stage and non-submandibular adenoid cystic carcinoma patients showed no survival benefit from adjuvant radiotherapy (aRT). These results underscore the role of tumor site on treatment response and survival of patients with head and neck ACC. Abstract Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor, displaying aggressive behavior with frequent recurrence and metastasis. Little information exists regarding the impact of clinicopathological parameters and adjuvant radiotherapy (aRT) on ACC disease specific (DSS) and overall survival (OS). We extracted demographic, treatment, and survival information of 1439 patients with major or minor intraoral salivary gland ACC from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between tumor characteristics and aRT with OS and DSS were estimated using hazard ratios (HR) and 95% confidence intervals (CI). Submandibular gland ACCs had the worst prognosis (adjusted DSS HR = 1.48; 95% CI = 0.99–2.20, compared to parotid), and this difference was more pronounced among patients with advanced-stage tumors (adjusted DSS HR = 1.93; 95% CI = 1.13–3.30). aRT was associated with increased overall survival only among stage III submandibular ACC patients (HR = 0.64; 95% CI = 0.42–0.98) and had no benefit in any other group. In conclusion, submandibular gland ACC carries a worse prognosis than other gland subsites and may benefit from aRT. The different outcomes between submandibular gland and other major or minor gland ACCs warrant further mechanistic investigation.
Alpha-1 antitrypsin deficiency impairs lung antibacterial immunity in mice

Alpha-1 antitrypsin (AAT) is a major inhibitor of serine proteases in mammals. Therefore, its deficiency leads to protease–antiprotease imbalance and a risk for developing lung emphysema. Although therapy with human plasma-purified AAT attenuates AAT deficiency–related emphysema, its impact on lung antibacterial immunity is poorly defined. Here, we examined the effect of AAT therapy on lung protective immunity in AAT-deficient (KO) mice challenged with Streptococcus pneumoniae. AAT-KO mice were highly susceptible to S. pneumoniae, as determined by severe lobar pneumonia and early mortality. Mechanistically, we found that neutrophil-derived elastase (NE) degraded the opsonophagocytically important collectins, surfactant protein A (SP-A) and D (SP-D), which was accompanied by significantly impaired lung bacterial clearance in S. pneumoniae–infected AAT-KO mice. Treatment of S. pneumoniae–infected AAT-KO mice with human AAT protected SP-A and SP-D from NE-mediated degradation and corrected the pulmonary pathology observed in these mice. Likewise, treatment with Sivelestat, a specific inhibitor of NE, also protected collectins from degradation and significantly decreased bacterial loads in S. pneumoniae–infected AAT-KO mice. Our findings show that NE is responsible for the degradation of lung SP-A and SP-D in AAT-KO mice affecting lung protective immunity in AAT deficiency.
Efficacy of external fixation of a straight silicone stent in the treatment of subglottic stenosis.

BACKGROUND The incidence of subglottic stenosis is rising year by year. For this difficult clinical problem, the efficacies of surgical and bronchoscopic intervention treatments vary. A simple and effective method to affix silicone stents is needed for the treatment of subglottic stenosis. METHODS Eight patients suffering from subglottic stenosis underwent straight silicone stent placement with external fixation in the First Affiliated Hospital of Chengdu Medical College between January 2015 and August 2019. All patients received regular postoperative bronchoscopy. A retrospective analysis was conducted to analyze the efficacy and complications of the operation. RESULTS Straight silicone stent placement was successful in seven patients and the external fixation of stents was completed. Symptoms of dyspnea were resolved in seven cases (87.5%), and the mean diameter of the upper trachea was significantly increased from 3.54±0.59 to 12.71±2.42 mm after the operation (t=15.78, P=0.002). The modified Medical Research Council dyspnea scale score significantly decreased from 3.4 (2.7, 3.8) to 0.8 (0.4, 1.4) after the operation (Z=-6.63, P=0.001). Postoperative complications were observed, including one case of mediastinal emphysema and pneumothorax, two cases of granulation tissue hyperplasia, four cases of intractable cough, six cases of postoperative infection at the external fixation site, one case of postoperative bleeding, and one case of sputum retention. All were promptly treated and quickly controlled. No stent displacement was observed during follow-up. CONCLUSIONS External fixation of straight silicon stents for the treatment of subglottic stenosis had good short-term outcomes and stable stent fixation. The proportion of postoperative infections was high. Therefore, the advantages and disadvantages of this operation need to be considered.
Circulating tumour DNA in B‐cell lymphomas: current state and future prospects

Circulating tumour DNA (ctDNA) is a highly versatile analyte and an emerging biomarker for detection of tumour‐specific sequences in lymphoid malignancies. Since ctDNA is derived from tumour cells throughout the body, it overcomes fundamental limitations of tissue biopsies by capturing the complete molecular profile of tumours, including those from inaccessible anatomic locations. Assays for ctDNA are minimally invasive and serial sampling monitors the effectiveness of therapy and identifies minimal residual disease below the detection limit of standard imaging scans. Dynamic changes in ctDNA levels measure real‐time tumour kinetics, and early reductions in ctDNA during treatment correlate with clinical outcomes in multiple B‐cell lymphomas. After therapy, ctDNA can effectively discriminate between patients who achieved a complete molecular remission from those with residual treatment‐resistant disease. Serial monitoring of ctDNA after therapy can detect early molecular relapse and identify drug‐resistant clones that harbour targetable mutations. In order for ctDNA to reach its full potential, the standardization and harmonization of the optimal pre‐analytical and analytical techniques for B‐cell lymphomas is a critically necessary requirement. Prospective validation of ctDNA within clinical studies is also required to determine its clinical utility as an adjunctive decision‐making tool.
The Role of ND10 Nuclear Bodies in Herpesvirus Infection: A Frenemy for the Virus?

Nuclear domains 10 (ND10), a.k. a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses. The diversity and dynamics of ND10 residents enable them to play seemingly opposite roles under different physiological conditions. Although the molecular mechanisms are not completely clear, the pro- and anti-cancer effects of ND10 have been well established in tumorigenesis. However, in herpesvirus research, until the recently emerged evidence of pro-viral contributions, ND10 nuclear bodies have been generally recognized as part of the intrinsic antiviral defenses that converge to the incoming viral DNA to inhibit the viral gene expression. In this review, we evaluate the newly discovered pro-infection influences of ND10 in various human herpesviruses and analyze their molecular foundation along with the traditional antiviral functions of ND10. We hope to shed light on the explicit role of ND10 in both the lytic and latent cycles of herpesvirus infection, which is imperative to the delineation of herpes pathogenesis and the development of prophylactic/therapeutic treatments for herpetic diseases.
Transcription activation depends on the length of the RNA polymerase II C‐terminal domain

Eukaryotic RNA polymerase II (Pol II) contains a tail‐like, intrinsically disordered carboxy‐terminal domain (CTD) comprised of heptad‐repeats, that functions in coordination of the transcription cycle and in coupling transcription to co‐transcriptional processes. The CTD repeat number varies between species and generally increases with genome size, but the reasons for this are unclear. Here, we show that shortening the CTD in human cells to half of its length does not generally change pre‐mRNA synthesis or processing in cells. However, CTD shortening decreases the duration of promoter‐proximal Pol II pausing, alters transcription of putative enhancer elements, and delays transcription activation after stimulation of the MAP kinase pathway. We suggest that a long CTD is required for efficient enhancer‐dependent recruitment of Pol II to target genes for their rapid activation.
The C3/465 glycan hole cluster in BG505 HIV-1 envelope is the major neutralizing target involved in preventing mucosal SHIV infection

Stabilized HIV-1 envelope (Env) trimers elicit tier 2 autologous neutralizing antibody (nAb) responses in immunized animals. We previously demonstrated that BG505 SOSIP.664. T332N gp140 (BG505 SOSIP) immunization of rhesus macaques (RM) provided robust protection against autologous intra-vaginal simian-human immunodeficiency virus (SHIV) challenge that was predicted by high serum nAb titers. Here, we show that nAb in these protected RM targeted a glycan hole proximal to residue 465 in gp120 in all cases. nAb also targeted another glycan hole at residues 241/289 and an epitope in V1 at varying frequencies. Non-neutralizing antibodies directed at N611-shielded epitopes in gp41 were also present but were more prevalent in RM with low nAb titers. Longitudinal analysis demonstrated that nAb broadened in some RM during sequential immunization but remained focused in others, the latter being associated with increases in nAb titer. Thirty-eight monoclonal antibodies (mAbs) isolated from a protected RM with an exceptionally high serum neutralization titer bound to the trimer in ELISA, and four of the mAbs potently neutralized the BG505 Env pseudovirus (PV) and SHIV. The four neutralizing mAbs were clonally related and targeted the 465 glycan hole to varying degrees, mimicking the serum. The data demonstrate that the C3/465 glycan hole cluster was the dominant neutralization target in high titer protected RM, despite other co-circulating neutralizing and non-neutralizing specificities. The isolation of a neutralizing mAb family argues that clonotype expansion occurred during BG505 SOSIP immunization, leading to high titer, protective nAb and setting a desirable benchmark for HIV vaccines.
Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single‐cell profiling

Similar to the brain, the eye is considered an immune‐privileged organ where tissue‐resident macrophages provide the major immune cell constituents. However, little is known about spatially restricted macrophage subsets within different eye compartments with regard to their origin, function, and fate during health and disease. Here, we combined single‐cell analysis, fate mapping, parabiosis, and computational modeling to comprehensively examine myeloid subsets in distinct parts of the eye during homeostasis. This approach allowed us to identify myeloid subsets displaying diverse transcriptional states. During choroidal neovascularization, a typical hallmark of neovascular age‐related macular degeneration (AMD), we recognized disease‐specific macrophage subpopulations with distinct molecular signatures. Our results highlight the heterogeneity of myeloid subsets and their dynamics in the eye that provide new insights into the innate immune system in this organ which may offer new therapeutic targets for ophthalmological diseases.
Identification of Central and Stretch Reflex Contributions to Human Postural Control

Human postural control requires continuous modulation of ankle torque to stabilize the upright stance. The torque is generated by two components: active contributions, due to central control and stretch reflex, and passive mechanisms, due to joint intrinsic stiffness. Identifying the contribution of each component is difficult, since their effects appear together, and standing is controlled in closed-loop. This article presents a novel multiple-input, single-output method to identify central and stretch reflex contributions to human postural control. The model uses ankle muscle EMGs as inputs and requires no kinematic data. Application of the method to data from nine subjects during standing while subjected to perturbations of ankle position demonstrated that active torque accounted for 84.0± 5.5% of the ankle torque. The ankle plantar-flexors collectively produced the largest portion of the active torque through central control, with large inter-subject variability in the relative contributions of the individual muscles. In addition, reflex contribution of the plantar-flexors was substantial in half of the subjects, showing its potentially important functional role; finally, intrinsic contributions, estimated as the residual of the model, contributed to 15% of the torque. This study introduces a new method to quantify the contributions of the central and stretch reflex pathways to postural control; the method also provides an estimate of noisy intrinsic torque with significantly increased signal to noise ratio, suitable for identification of intrinsic stiffness in standing. The method can be used in different experimental conditions and requires minimal a-priori assumption regarding the role of different pathways in postural control.