Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

Nonabelian Ginzburg-Landau theory for ferroelectrics.

The Ginzburg-Landau theory, which was introduced to phenomenologically describe the destruction of superconductivity by a magnetic field at the beginning, has brought up much more knowledge beyond the original one as a mean-field theory of thermodynamics states. There the complex order parameter plays an important role. Here we propose a macroscopic theory to describe the features of ferroelectrics by a two-component complex order parameter coupled to nonabelian gauge potentials that provide more freedom to reflect interplays between different measurables. Within this theoretical framework, some recently discovered empirical static and time-independent phenomena, such as vortex, anti-vortex, spiral orders can be obtained as solutions for different gauge potentials. It is expected to bring in a new angle of view with more elucidation than the traditional one that takes the polarization as order parameter.

Efficacy, toxicity, and quality-of-life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single-arm phase 2 trial from Asia.

AIMS: Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center. METHODS: We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT. RESULTS: Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A). CONCLUSION: UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa.

Assessment of probiotic adhesion and inhibitory effect on Escherichia coli and Salmonella adhesion.

In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.

Validation of Modified Breast Graded Prognostic Assessment for breast cancer patients with brain metastases: extra-cranial disease progression is an independent risk factor.

BACKGROUND: Breast cancer (BC) patients with brain metastases (BM) are heterogeneous with markedly variable survival. The Breast Graded Prognostic Assessment (B-GPA) and Modified B-GPA (mB-GPA) have been proposed as useful tools for stratifying survival in this population. However, extra-cranial disease progression, a clinically important variable, is not incorporated into the final model. We undertook the validation of B-GPA and mB-GPA in an Asian cohort and further explore extra-cranial disease progression as a prognostic factor. METHODS: Data of BC patients with newly diagnosed BM between 2006 and 2017 was extracted retrospectively from a prospectively maintained institutional database. Patients were classified based on their B-GPA and mB-GPA scores. Univariate (UVA) and multivariate analysis (MVA) using the Cox proportional hazard model were performed to investigate the factors prognostic of overall survival (OS). The Kaplan-Meier method was used to estimate OS and log-rank test to compare survival between scores. The performances of B-GPA and mB-GPA were compared using Harrell's concordance index (C-index) and Akaike information criterion (AIC). RESULTS: In our cohort of 282 patients, the B-GPA and mB-GPA were validated as prognostic tools for OS, demonstrating excellent separation between survival curves (P <0.001). In MVA, we found all components of mB-GPA (age, performance status, number of BM, tumour subtype) to be independent predictors of survival. C-index was 0.64 and AIC was 2,483.39 for B-GPA. mB-GPA demonstrated marginally better discrimination with a C-index of 0.65 and AIC of 2,445.78. Extra-cranial progression was an independent predictor for survival in our population (P <0.001). CONCLUSIONS: The mB-GPA incorporates four simple clinical variables each of independent prognostic significance. Both B-GPA and mB-GPA demonstrate moderate discriminative capabilities for OS with mB-GPA performing marginally better. Inclusion of extra-cranial disease progression as a factor in future model development may further improve its prognostic value.

Combinatorial strategies of radiotherapy and immunotherapy in nasopharyngeal carcinoma.

Immunotherapy and radiation therapy (RT) have each demonstrated clinical success in the treatment of nasopharyngeal carcinoma (NPC) when utilized independently. Several characteristics of NPC make it particularly well suited for immunotherapeutic strategies, such as the association with viral infections like EBV and human papilloma virus (HPV), upregulation of PD-L1 expression, and the high number of tumor infiltrating lymphocytes. Immune checkpoint blockade is one such immunotherapeutic strategy that is gaining popularity rapidly. However, clinical benefit of immunotherapy using immune checkpoint inhibitors has been limited to only a small subset of patients with existing T cell responses. Additionally, they are frequently associated with dose-limiting immune-related toxicities. On the other hand, RT is a conventional strategy for NPC treatment, which has demonstrated high efficacy in local tumor control and has also been reported to exhibit immune modulatory effects. However, the abscopal effect of RT alone, i.e., the regression of distant metastases outside of the irradiation field, remains a rare phenomenon. Furthermore, RT treatment efficacy is also limited by radioresistance and radiation-related toxicities. Hence, the combination of RT and immunotherapy has the potential to improve treatment efficacy over either individual therapies alone. Here, we reviewed the clinical problem in locally advanced and recurrent/metastatic NPC, and discussed how combinatorial RT and immunotherapeutic strategies can be relevant to NPC treatment in each clinical scenario by examining the underlying mechanisms involved in the different strategies.

A Rout to Protect Quantum Gates constructed via quantum walks from Noises.

The continuous-time quantum walk on a one-dimensional graph of odd number of sites with an on-site potential at the center is studied. We show that such a quantum-walk system can construct an X-gate of a single qubit as well as a control gate for two qubits, when the potential is much larger than the hopping strength. We investigate the decoherence effect and find that the coherence time can be enhanced by either increasing the number of sites on the graph or the ratio of the potential to the hopping strength, which is expected to motivate the design of the quantum gate with long coherence time. We also suggest several experimental proposals to realize such a system.

"Cor Occidere": a novel strategy of targeting the tumor core by radiosurgery in a radio- and chemo-resistant intracranial hemangiopericytoma.

Intracranial hemangiopericytomas (HPC) are chemotherapy- and radiotherapy (RT)-resistant. Here, we report on a novel stereotactic radiosurgery (SRS) technique-"Cor Occidere" (Latin), as a potential strategy of overcoming radioresistance of HPC. A 36-year old female presented to our clinic for consideration of a 3rd-course of RT for her recurrent cavernous sinus HPC, following previous cranial RT at 13 and 5 years prior, and a failed 9 months trial of bevacizumab/temozolomide. The tumor-adjacent brain stem and carotid artery risked substantial damage given the cumulative RT doses to these organs. We therefore designed an SRS plan targeting only the tumor core with 16 Gy single-fraction. Despite underdosing the tumor margin, we achieved stable disease over 25 months, contrasting her responses to systemic therapies. Achieving tumor control despite a suboptimal treatment that utilized high dose ablation of the tumor core suggests novel biological mechanisms to overcome radioresistance of HPC.

Prognostic Model for Stratification of Radioresistant Nasopharynx Carcinoma to Curative Salvage Radiotherapy.

Purpose To investigate for a prognostic index (PI) to personalize recommendations for salvage intensity-modulated radiotherapy (IMRT) in patients with locally recurrent nasopharyngeal carcinoma (lrNPC). Methods Patients with lrNPC from two academic institutions (Sun Yat-Sen University Cancer Center [SYSUCC-A; n = 251 (training cohort)] and National Cancer Centre Singapore [NCCS; n = 114] and SYSUCC-B [n = 193 (validation cohorts)]) underwent salvage treatment with IMRT from 2001 to 2015. Primary and secondary clinical end points were overall survival (OS) and grade 5 toxicity-free rate (G5-TFR), respectively. Covariate inclusion to the PIs was qualified by a multivariable two-sided P < .05. Discrimination and calibration of the PIs were assessed. Results The primary PI comprised covariates that were adversely associated with OS in the training cohort (gross tumor volumerecurrence hazard ratio [HR], 1.01/mL increase [ P < .001], agerecurrence HR, 1.02/year increase [ P = .008]; repeat IMRT equivalent dose in 2-Gy fractions [EQD2] ≥ 68 Gy HR, 1.42 [ P = .03]; prior radiotherapy-induced grade ≥ 3 toxicities HR, 1.90 [ P = .001]; recurrent tumor [rT]-category 3 to 4 HR, 1.96 [ P = .005]), in ascending order of weight. Discrimination of the PI for OS was comparable between training and both validation cohorts (Harrell's C = 0.71 [SYSUCC-A], 0.72 [NCCS], and 0.69 [SYSUCC-B]); discretization by using a fixed PI score cutoff of 252 determined from the training data set yielded low- and high-risk subgroups with disparate OS in the validation cohorts (NCCS HR, 3.09 [95% CI, 1.95 to 4.89]; SYSUCC-B HR, 3.80 [95% CI, 2.55 to 5.66]). Our five-factor PI predicted OS and G5-TFR (predicted v observed 36-month OS and G5-TFR, 22% v 15% and 38% v 44% for high-risk NCCS and 26% v 31% and 45% v 46% for high-risk SYSUCC-B). Conclusion We present a validated PI for robust clinical stratification of radioresistant NPC. Low-risk patients represent ideal candidates for curative repeat IMRT, whereas novel clinical trials are needed in the unfavorable high-risk subgroup.

Morphological Characteristics of Normal and Gynandromorphic Hyalomma asiaticum Schulze and Schlottke, 1930.

Gynandromorphic ticks are extremely rare, and often attract parasitologists' attention. During our examination of tick specimens, an engorged gynandromorph of Hyalomma asiaticum was noticed. This is the first record of gynandromorphic ticks from China. In this study, several important morphological structures of normal and gynandromorphic H. asiaticum were analyzed. Comparing to the normal H. asiaticum, the gynandromorphic specimen was a typical bipartite protogynander. Its right side showed normal female characteristics, whereas the left side had normal male traits. Different from other gynandromorphic ticks containing 1 anus, this tick reported here had 2 complete anuses, and the anus of the male part had a single adanal plate.

Spin-orbital driven ferroelectricity.

We study the effect of octahedron rotation on the electric polarization with spin-orbit coupling. Employing local coordinates to represent the tilting of the ligands' octahedra, we evaluate the electric polarization in a chain of transition metal ions with non-polar octahedron rotation. We find the orbital ordering produced by the ligands' rotation and the spin order, together, determine the polarization features, manifesting that non-vanishing polarization appears in collinear spin order and the direction of polarization is no more restricted in the plane of spin rotation in cycloidal ordering.

Molecular evidence for piroplasms in wild Reeves' muntjac (Muntiacus reevesi) in China.

DNA from liver samples of 17 free-ranging wild Reeves' muntjac (Muntiacus reevesi) was used for PCR amplification of piropalsm 18S rRNA gene. Of 17 samples, 14 (82.4%) showed a specific PCR product which were cloned and sequenced. BLAST analysis of the sequences obtained showed similarities to Babesia sp., Theileria capreoli, Theileria uilenbergi and Theileria sp. BO302-SE. Phylogenetic analysis showed that the Babesia sp. detected in the present study was distantly separated from known Babesia species of wild and domestic animals. Six sequences showed 100% similarity to T. capreoli while five sequences were separated from all known Theileria species and constituted an independent clade with Theileria sp. BO302-SE derived from roe deer in Italy; two sequences were close to T. uilenbergi with 97% similarity. This is the first description of hemoparasite infection in free-ranging wild Reeves' muntjac in China. Our results indicate that wild Reeves' muntjac may play an important reservoir role for hemoparasites.

Bond distortion effects and electric orders in spiral multiferroic magnets.

In this paper we study the bond distortion effect on the electric polarization in spiral multiferroic magnets based on cluster and chain models. The bond distortion breaks the inversion symmetry and modifies the d-p hybridization. Consequently, it will affect the electric polarization, which can be divided into the spin-current part and the lattice-mediated part. The spin-current polarization can be written in terms of [Formula: see text] with anisotropic amplitude, and the lattice-mediated polarization exists only when the M-O-M bond is distorted. The electric polarization for three-atom M-O-M and four-atom M-O2-M clusters is calculated. We also study possible electric ordering in three kinds of chains made of different clusters. We apply our theory to multiferroic cuprates and find that the results are qualitatively in agreement with experimental observations.

A mechanism to pin skyrmions in chiral magnets.

We propose a mechanism to pin skyrmions in chiral magnetic thin films by introducing local maxima of magnetic exchange strength as pinning centers. The local maxima can be realized by engineering the local density of itinerant electrons. The stationary properties and the dynamical pinning and depinning processes of an isolated skyrmion around a pinning center are studied. We carry out numerical simulations of the Landau-Lifshitz-Gilbert (LLG) equation and find a way to control the position of an isolated skyrmion in a pinning center lattice using electric current pulses. The results are verified by a Thiele equation analysis. We also find that the critical current to depin a skyrmion, which is estimated to have order of magnitude 10(7)-10(8) A m(-2), has linear dependence on the pinning strength.

The splitting of the electromagnon mode in conically spiral multiferroic magnets.

In this paper, we study conically spiral multiferroic magnets with coupled magnetic and ferroelectric orders. By generalizing the spin-current model, we study spin wave excitations and electromagnons. We find that the electromagnon mode will split into two branches with different dispersions in an (external or internal) magnetic field. We apply our theory to some multiferroic materials and find that the results qualitatively agree with recent experiments. We also make predictions for new experiments.

Polymorphism analysis of Chinese Theileria sergenti using allele-specific polymerase chain reaction of the major piroplasm surface protein gene.

Theileria sergenti is a tick-borne parasite found in many parts of the world. The major piroplasm surface protein (MPSP), a conserved protein in all Theileria species, has been used as a marker for epidemiological and phylogenetic studies of benign Theileria species. In this study, Chinese species of T. sergenti were characterized by allele-specific polymerase chain reaction (PCR) and DNA sequence analysis of the MPSP gene. Using universal or allele-specific primer sets for PCR amplification of the MPSP gene, 98 of 288 cattle blood samples, collected from 6 provinces in China, were found to be positive. Among the positive samples, only 3 allelic MPSP gene types (Chitose [C]-, Ikeda [I]-, and buffeli [B]-type) were successfully amplified. Moreover, the results revealed that the majority of the parasites sampled in this study were C- and I-type (prevalence of 84 and 69%, respectively), whereas the B-type was less common (prevalence of 36%). Co-infections with C-, I-, and B-type T. sergenti also were found. An additional known allele, Thai-type, was not detected. Phylogenetic analysis based on the MPSP gene sequences, including 3 standard stocks generated in the laboratory ( T. sergenti Wenchuan, T. sergenti Ningxian, and T. sergenti Liaoyang), revealed that the isolates of Chinese sergenti were comprised of at least 4 allelic MPSP gene types, i.e., C-, I-, B1-, and B2-type, and these parasites with 6 MPSP types 1-5 and 7 were present in China.

Phase I Study to Determine MTD of Docetaxel and Cisplatin with Concurrent Radiation Therapy for Stage III Non-Small Cell Lung Cancer.

OBJECTIVE: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2-4 cycles of induction chemotherapy. METHODS: Fourteen patients with histological/cytological proven stage III non-small-cell lung cancer were eligible. 3D or IMRT radiotherapy (60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction) was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy (CCRT). The level I dosage was composed of 56 mg/m(2) DCT, on day 1 and 28mg/m(2) DDP, on day 1 and day 2. The level II was composed of 60 mg/m(2) DCT, on day 1 and 30 mg/ m(2) DDP, on day 1 and day 2. The level III was composed of 64 mg/m(2) DCT, on day 1 and 32 mg/ m(2) DDP, on day 1 and day 2. RESULTS: Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III (64 mg/m(2)) and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. CONCLUSIONS: Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m(2) docetaxel and 60mg/m(2) cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.

Sequence analysis of Theileria annulata surface protein in Chinese isolates.

OBJECTIVE: To study the TaSP polymorphism in three Chinese isolates of Theileria annulata. METHODS: The isolates from Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region and Xinjiang Uygur Autonomous Region were cultured in RPMI 1640 medium. TaSP gene was amplified from genomic DNA extracted from schizonts using polymerase chain reaction (PCR) and sequenced. Its amino acid sequence comparison was carried out with Clustal W2 multiple sequence alignment program. Molecular component and motif prediction were performed with online servers. RESULTS: The comparison of TaSP amino acid sequences of the three isolates showed that the central region (aa position 38-161) predicted to be the highly immunogenetic domain was polymorphic both in size and amino acid sequence, while the N-terminal (first 37 aa) and C-terminal (last 154 aa) parts were strongly conserved. Phylogenetic analysis and percentage identity revealed that the Chinese isolates were closely related to the isolates from Turkey, but quite different from those of India, Morocco and Tunisia. More importantly, variability was noticed among Chinese isolates, which caused both the location and number's differences of motif (casein kinase II phosphorylation sites) among three TaSP sequences. CONCLUSION: TaSP polymorphism exists in the Chinese isolates of T. annulata.

The role of secondary structure in protein structure selection.

The presence of highly regular secondary structure motifs in protein structure is a fascinating area of study. The secondary structures play important roles in protein structure and protein folding. We investigate the folding properties of protein by introducing the effect of secondary structure elements. We observed the emergence of several structures with both large average energy gap and high designability. The dynamic study indicates that these structures are more foldable than those without the effect of secondary structures.