FLASH radiotherapy for the treatment of symptomatic bone metastases in the thorax (FAST-02): protocol for a prospective study of a novel radiotherapy approach.

BACKGROUND: FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates (≥ 40 Gy/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting. METHODS: This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1-3 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8 Gy in a single fraction administered at ≥ 40 Gy/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table. DISCUSSION: This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent. REGISTRATION: ClinicalTrials.gov NCT05524064.

Enhancement of progesterone biosynthesis via kisspeptin stimulation: Upregulation of steroidogenic transcripts and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) expression in the buffalo luteal cells.

The presence of Kisspeptin (Kp) and its receptors in the corpus luteum (CL) of buffalo has recently been demonstrated. In this study, we investigated the role of Kp in the modulation of progesterone (P4) synthesis in vitro. The primary culture of bubaline luteal cells (LCs) was treated with 10, 50, and 100 nM of Kp and Kp antagonist (KpA) alongside a vehicle control. The combined effect of Kp and KpA was assessed at 100 nM concentration. Intracellular response to Kp treatment in the LCs was assessed by examining transcript profiles (LHR, STAR, CYP11A1, HSD3B1, and ERK1/2) using quantitative polymerase chain reaction (qPCR). In addition, the immunolocalization of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in the LCs was studied using immunocytochemistry. Accumulation of P4 from the culture supernatant was determined using enzyme-linked immunosorbent assay (ELISA). The results indicated that LCs had a greater p-ERK1/2 expression in the Kp treatment groups. A significant increase in the P4 concentration was recorded at 50 nM and 100 nM Kp, while KpA did not affect the basal concentration of P4. However, the addition of KpA to the Kp-treated group at 100 nM concentration suppressed the Kp-induced P4 accumulation into a concentration similar to the control. There was significant upregulation of ERK1/2 and CYP11A1 expressions in the Kp-treated LCs at 100 nM (18.1 and 37fold, respectively, p < 0.01). However, the addition of KpA to Kp-treated LCs modulated ERK1/2, LHR, STAR, CYP11A1, and HSD3B1 at 100 nM concentration. It can be concluded that Kp at 100 nM stimulated P4 production, while the addition of KpA suppressed Kp-induced P4 production in the buffalo LCs culture. Furthermore, an increment in p-ERK1/2 expression in the LCs indicated activation of the Kp signaling pathway was associated with luteal steroidogenesis.

Multi-omics analysis identifies potential microbial and metabolite diagnostic biomarkers of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common clinical manifestation of a perturbed vaginal ecology associated with adverse sexual and reproductive health outcomes if left untreated. The existing diagnostic modalities are either cumbersome or require skilled expertise, warranting alternate tests. Application of machine-learning tools to heterogeneous and high-dimensional multi-omics datasets finds promising potential in data integration and may aid biomarker discovery. OBJECTIVES: The present study aimed to evaluate the potential of the microbiome and metabolome-derived biomarkers in BV diagnosis. Interpretable machine-learning algorithms were used to evaluate the utility of an integrated-omics-derived classification model. METHODS: Vaginal samples obtained from reproductive-age group women with (n = 40) and without BV (n = 40) were subjected to 16S rRNA amplicon sequencing and LC-MS-based metabolomics. The vaginal microbiome and metabolome were characterized, and machine-learning analysis was performed to build a classification model using biomarkers with the highest diagnostic accuracy. RESULTS: Microbiome-based diagnostic model exhibited a ROC-AUC (10-fold CV) of 0.84 ± 0.21 and accuracy of 0.79 ± 0.18, and important features were Aerococcus spp., Mycoplasma hominis, Sneathia spp., Lactobacillus spp., Prevotella spp., Gardnerella spp. and Fannyhessea vaginae. The metabolome-derived model displayed superior performance with a ROC-AUC of 0.97 ± 0.07 and an accuracy of 0.92 ± 0.08. Beta-leucine, methylimidazole acetaldehyde, dimethylethanolamine, L-arginine and beta cortol were among key predictive metabolites for BV. A predictive model combining both microbial and metabolite features exhibited a high ROC-AUC of 0.97 ± 0.07 and accuracy of 0.94 ± 0.08 with diagnostic performance only slightly superior to the metabolite-based model. CONCLUSION: Application of machine-learning tools to multi-omics datasets aid biomarker discovery with high predictive performance. Metabolome-derived classification models were observed to have superior diagnostic performance in predicting BV than microbiome-based biomarkers.

Mito-Q supplementation of in vitro maturation or in vitro culture medium improves maturation of buffalo oocytes and developmental competence of cloned embryos by reducing ROS production.

Mito-Q is a well-known mitochondria-specific superoxide scavenger. To our knowledge, the effect of Mito-Q on buffalo oocyte maturation and developmental competency of cloned embryos has not been examined. To investigate the effects of Mito-Q on the in vitro maturation (IVM) of buffalo oocytes and the developmental competence of cloned embryos, different concentration of Mito-Q were supplemented with IVM (0, 0.1, 0.5, 1, 2 µM) and in vitro culture (IVC) medium (0, 0.1 µM). Supplementation of IVM medium with 0.1 µM Mito-Q significantly (P ≤ 0.05) increased the cumulus expansion, nuclear maturation, mitochondrial membrane potential (MMP) and antioxidants genes (GPX1 and SOD2) expression and effectively reduced ROS production leading to a significant improvement in the maturation rate of buffalo oocytes. Further, the supplementation of 0.1 µM Mito-Q in IVC medium promotes the cleavage and blastocyst rate significantly over the control. Mito-Q supplementation improves (P ≤ 0.05) MMP, antioxidant gene (GPX1) expression and reduced the ROS level and apoptosis related genes (caspase 9) expression in cloned blastocysts. In conclusion, the present study demonstrated that the supplementation of 0.1 µM Mito-Q in IVM and IVC media exerts a protective role against oxidative stress by reducing ROS production and improving MMP, fostering improved maturation of buffalo oocytes and enhanced developmental competence of cloned embryos. These findings contribute valuable insights into the optimization of assisted reproductive technologies protocols for buffalo breeding and potentially offer novel strategies to enhance reproductive outcomes in livestock species.

Is Brucella excreted in cattle faeces? - Evidence from Punjab, India.

Brucellosis is a neglected zoonosis that affects animals and people in much of the underdeveloped world. The disease is endemic in cattle in Punjab, India and controlling it is a public health challenge. Dairy farmers and farm labour commonly handle cattle faeces with bare hands and personal protective equipments are not used. No studies have been conducted about the shedding of Brucella species in faeces of sero positive cattle in the state. This study aimed to isolate and identify the Brucella species from faeces of sero positive cattle in Punjab, India. Faecal samples were collected from 350 Brucella sero positive cattle in Ludhiana district of Punjab, India. Isolation was performed using a pre-enriched Brucella selective broth medium as well as Brucella selective medium agar plates containing horse serum and Brucella selective supplements. Isolates were identified using Gram staining technique and rapid slide agglutination test, and then confirmed by using bcsp31 and 16s rRNA genus specific PCR. Isolates were further identified up to species level by using Bruce-Ladder multiplex PCR. Fourteen Brucella species were isolated, all of which showed coccobacilli on gram staining, positive rapid slide agglutination test and amplification of bcsp31 and 16s rRNA genes. Of the 14 isolates, 11 were identified as Brucella abortus and 3 were identified as Brucella melitensis. The study demonstrates that animal faeces could pose a potential risk for animal and human health and faeces of seropositive cattle must be handled with care.

Effect of membrane stabilizers on semen quality and sperm membrane protein expression during cryopreservation of goat semen.

BACKGROUND: Semen cryopreservation is a complex process during which there is alteration in the expression of sperm and seminal plasma proteins, molecular weight of protein or loss of membrane proteins during the process. In order to compensate for these changes, different membrane stabilizers are used in freezing semen extenders. However, there is scarcity of such studies during cryopreservation of goat semen. OBJECTIVE: To investigate the effect of membrane stabilizers on sperm membrane protein expression during cryopreservation of goat semen. MATERIALS AND METHODS: A total of 36 semen ejaculates from nine Assam Hill Goat bucks aged 2 to 2.5 years was collected by artificial vagina method. Three membrane stabilizers, each at two different concentrations viz. 50 and 80 mM sucrose, 50 and 100 mM trehalose, and 100 and 150 ng per mL IGF-1 (insulin-like growth factor 1 protein) were added to Tris-citric acid fructose egg yolk glycerol (TCFEYG) extender and semen samples were cryopreserved. The sperm membrane protein profile was studied in fresh and cryopreserved semen by SDS-PAGE. RESULTS: SDS- PAGE of sperm membrane extract of fresh semen revealed the presence of 24 protein bands with molecular weights ranging from 10 kDa to 240 kDa. Samples supplemented with 50 mM sucrose and 80 mM sucrose revealed 21 protein bands with molecular weights ranging from 10 kDa to 240 kDa. All the 21 protein bands were same as those observed in the sperm membrane of fresh spermatozoa, except that the 23 kDa, 29 kDa and 42 kDa bands were absent in frozen semen. Similarly, frozen semen extended with 50 mM trehalose and 100 mM trehalose revealed 22 protein bands with molecular weights ranging from 10 kDa to 240 kDa, but lacking the 29 kDa and 42 kDa bands. Proteins with molecular weights of 29 kDa, 130 kDa and 240 kDa were absent in frozen semen supplemented with 100 ng per mL IGF-1 and 150 ng per mL IGF-1. CONCLUSION: The present study revealed that supplementation of tris basic extender with trehalose at 100 mM and or IGF-1 at 100 ng/mL or 150 ng per mL improves the post-thaw semen characteristics and protects certain fertility related sperm membrane proteins. Doi.org/10.54680/fr23510110612.

Assessing Spectrum of Fractures in Elderly; Perspective on Tertiary Care Hospital of Nepal.

Background There is an increasing life expectancy and a surging elderly population in the last few decades, leading to a higher incidence of fractures in the elderly. The health care of the elderly in Nepal is below par and there are no studies done to evaluate the spectrum of fractures in the elderly. Objective To evaluate the demographical and epidemiological aspects of fractures in the elderly (≥ 65 years) presenting to a tertiary care hospital in Nepal in a 15 years' timeline. Method This study was a retrospective epidemiological study conducted in the Department of Orthopedics, Dhulikhel Hospital, Kathmandu University Hospital (DH, KUH), Nepal. The patients of age ≥ 65 years having traumatic injuries, admitted in the orthopedics ward from 2006 January to 2020 December were included. Patient demographics, site of injury, fracture incidence, mechanism of injury, hospital stay duration, and mode of treatment (surgical/ conservative) were evaluated. Result Of the 787 patients with an average age of 73.65 ± 7.5 years, 54% were females. Peritrochanteric fracture was the most common fracture (29.4%) followed by spine (18.3%). The most common mechanism of injury was fall on the labeled ground (38.6%). The incidence of fragility fractures (peri-trochanteric, proximal humerus, spine, and distal radius) was increasing with age. Conclusion Females, peritrochantric fractures, and trivial trauma are the most common occurrences for fractures in elderly. The incidence of fragility fractures is increasing with age but the overall incidence of fractures compared to other studies is low. Higher incidences of road traffic accidents (RTA) and compound fractures among the elderly are serious public health concerns that highlight the importance of primary preventive measures.

Comparative evaluation of native top feeds of western Himalayas for utilization as goat's ration in mash and block form.

The current research was undertaken to scrutinize the effect of leaf meal mixture as concentrate mixture in the ration of goats. Leaf meal mixture (LMM) was prepared using equal quantities of ten top-foliages namely Acacia nilotica, Celtis australis, Ficus palmata, Ficus religiosa, Grewia optiva, Melia azadarach, Morus alba, Quercus incana, Salix alba and Zizyphus jujube obtained from district Poonch of Jammu region in western Himalayas. The LMM prepared was substituted for 15% in the concentrate mixture being fed to the goats. The study constituted of two trials. Concentrate mixture offered to the animals was in mash and multi-nutrient block in first and second trial respectively. A total of twelve non-descript, adult male goats were selected for each trial. Goats of 0-14 months age (27.71 ± 2.96 kg live body weight) of for first trial while goats of 12-16 months age (27.02 ± 2.93 kg live weight) for second trial were divided into control and treatment groups as per randomized block design and fed ad-lib wheat straw and concentrate mixture @ (20 g/kgW0.75). No significant variation was observed (p > 0.05) in body weight, feed and DM intake among all groups in both trials. Comparable intake as well as digestibility of various nutrients like DM, OM, CP, EE, CF, NFE, NDF, ADF and TDN were found between the two groups during individual trials. There was a positive nitrogen, calcium and phosphorus balance among all experimental animals in both the trials. Serum enzymes ALT, AST and haemato-biochemical parameters like total protein, albumin, globulin, albumin: globulin and blood urea nitrogen (BUN) showed no significant differences during both trials in all groups, being within normal physiological levels. However, haemoglobin concentration was significantly higher (P < 0.05) in treatment group with respect to the control group in first trial. On the basis of current results, it can be established that leaf meal mixture can successfully be used to replace concentrate mixture up to 15% in the ration of goats without expecting any adverse impacts on their growth and overall health.

Prevalence of Brucella species in stray cattle, dogs and cats: A systematic review.

Stray animals are unowned free roaming, homeless, abandoned, street or sheltered animals, particularly dogs, cats and cattle. They could act as carrier of several zoonotic pathogens such as rabies virus, Mycobacterium and Brucella species. However, comprehensive information on the prevalence of zoonotic pathogens in stray animals is very limited. We conducted a systematic review as per Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines to estimate the prevalence of brucellosis in stray dogs, cats and cattle. Eligibility criteria for the study were determined using the PECOS classification (population, exposure, comparison, outcome, study design) as a tool to guide the research and adjust the search strategy. Major bibliographic databases [Web of Science, Medline, Scopus, ScienceDirect, Google Scholar and PubMed] were searched using predefined keywords for published epidemiological studies on brucellosis in stray animals (dogs, cats and cattle). Systematic assessments of all the studies since 1990-2022 were conducted and those reporting the prevalence of brucellosis in stray dogs, cats and cattle using appropriate diagnostic tests (culture, molecular, serological) were included. Studies reporting prevalence of brucellosis (Brucella infection or exposure) in kennel dogs, dairy herds, livestock farms, humans or marine species were excluded. The apparent individual test- wise prevalence along with 95% confidence intervals (CI) was estimated using Epitools. Out of 2689 studies, 37 met the inclusion criteria and were included in the systematic review. Of 37 studies, 28 (75.7%) were conducted in stray dogs, 7 (18.9%) in cattle and 2 (5.4%) in cats. Furthermore, only 21.62% studies (8/37) used probabilistic random sampling approaches and 13.51% studies (5/37) explained and justified the study sample size using appropriate methods for estimation of disease prevalence in the study populations. Higher sero-prevalence in stray dogs has been reported in studies conducted in Jordan (38.0% (95% CI: 24.0-54.0) and Pakistan (38.0% (95% CI: 31.0-45.0) whereas no sero-positivity was recorded in the studies conducted in Brazil, North Colombia, Cyprus, South Korea and USA. All studies on brucellosis (n = 7) in stray cattle were from India; conducted in stray cattle reared in cow-shelters. Sero-prevalence in the range of 4.3%- 64.3% was reported in stray cattle. Differences in diagnostic tests and host species, as well as limited number and non-randomized studies and high statistical heterogeneity did not allow us to determine combined meta-analysed prevalence estimates. Stray animals are likely to pose a zoonotic and disease spillover risk to human and livestock populations.

Functional hBN decorated Ni(OH)2 nanosheets synthesized for remarkable adsorption performance for the elimination of fluoride ions.

Occurrence of fluoride in groundwater is a serious concern due to its fatal effects. Functionalized hexagonal boron nitride sheets have been combined with nickel hydroxide nanoparticles by a one step process and a hybrid adsorbent Ni(OH)2@hBN has been developed with an exceptionally high fluoride adsorption capacity of 365 mg g-1, higher than those of Ni(OH)2 and hBN. This maximum adsorption capacity is higher than those of most common adsorbents used for defluoridation including activated alumina, reported nickel oxide and carbon-based 2D material-supported alumina adsorbents. The presence of functionalized boron nitride significantly increased the surface area to 680 m2 g-1 with a pore volume of 0.33687 cm3 g-1 and provided rich hydroxyl group-containing surface sites for the removal of fluoride present in contaminated water. In addition, the adsorption of fluoride onto boron nitride-modified nickel hydroxide followed pseudo-second-order kinetics and the equilibrium data fitted well with the Langmuir adsorption isotherm, suggesting a monolayer adsorption mechanism. Furthermore, the material developed is tested with the water sample collected from a real affected area, from the Dhar district of India, and the material showed promising results in terms of fluoride removal efficacy.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

Prevalence and risk factor investigation for exposure to Brucella species in surrogate stray cattle population reared in cow shelters in Punjab, India.

Bovine brucellosis is endemic in cattle in India, however not much is known on the prevalence of this disease in stray cattle populations of the country. This study aimed to estimate the prevalence and identify risk factors associated with brucellosis in the stray cattle populations reared in cow shelters (gaushalas) of Punjab, India. Blood samples were collected from 587 cattle reared in 23 cow shelters in 23 districts (one per district) of the Punjab and were tested using Rose Bengal plate test (RBPT), standard tube agglutination test (STAT) and Indirect Enzyme Linked Immunosorbent Assay (i-ELISA). Information on the sex and breed of the animal, total cattle population and presence of a separate shed for parturition were collected. An animal was considered exposed to Brucella infection based on a positive RBPT or STAT test and a positive i-ELISA test. Explanatory variables for the animal level disease status outcome variable were sex and breed of the animal and at the shelter level were shelter cattle population size and presence of a separate shed for parturition. Univariable binomial exact logistic regression analysis was conducted to assess the association of each explanatory variable with the binary outcome variable. Sixty-two animals were seropositive on RBPT, with an apparent seroprevalence of 10.56% (95% confidence interval [CI]: 8.33%, 13.31%) and the estimated true seroprevalence of 11.48% (95% CI: 8.9%, 14.64%). Sixty three animals were seropositive using STAT [apparent seroprevalence of 10.73% (95% CI: 8.48%, 13.50%) and the estimated true seroprevalence of 10.69% (95% CI: 8.27%, 13.67%)], and 68 using i-ELISA [an apparent seroprevalence of 11.58% (95% CI: 9.24%, 14.43%) and the estimated true seroprevalence of 13.28% (95% CI: 10.50%, 16.66%)]. Cross bred cattle had a lower risk of being test positive (odds ratio 0.16, p = 0.04) as compared to indigenous cattle. Due to a ban on cow slaughter in the country, roaming stray cattle infected with brucellosis present a permanent risk of introduction of disease to the dairy farms and other vulnerable populations.

Genetic analysis for semen quality traits in buffalo bulls.

This study was attempted to estimate the genetic parameters of semen quality traits in buffalo bulls. The study data consisted of 10975 ejaculates from 45 Murrah buffalo bulls (aged 24-72 months) used for breeding program during year 2010 to 2020. Semen quality traits (ejaculate volume, concentration of sperm, mass activity, initial and post-thaw motility, number of sperms per ejaculate, motile sperm number and discard rates) were studied. It was observed that average ejaculate volume was 2.82 ± 1.45 mL with mean concentration of 1040.12 ± 523.26 million/mL. Higher heritability was observed for number of sperms per ejaculate, number of motile sperm and sperm concentration. Significant phenotypic correlation was obtained between volume and number of sperms per ejaculate as well as volume and number of motile sperms. Likewise, significant phenotypic correlation was evident between sperm concentration with sperm number per ejaculate. Highest phenotypic correlation was obtained between sperm count per ejaculate and motile sperm count. Estimated genetic trends showed significant change in volume and motile sperm number. In conclusion, this study ascertains that genetic parameters of semen traits can be considered during the selection of buffalo bulls in breeding program.

Superior Interfacial Contact Yields Efficient Electron Transfer Rate and Enhanced Solar Photocatalytic Hydrogen Generation in M/C3N4 Schottky Junctions.

Various literature studies (Table 6) have reported that dispersion of metal nanoparticles (NPs) on graphitic carbon nitride g-C3N4 (M/CN) has considerably improved the photocatalytic hydrogen yield. It is understood that metal NPs create active sites on the surface of CN and act as a cocatalyst. However, the precise changes induced by different metal NPs on the surface of CN still elude us. Here, we report a thorough understanding and comparison of the morphology, metal-support interactions, interfacial charge transfer kinetics, and band characteristics in different M/CN (M = Pt, Pd, Au, Ag, Cu) correlated with photocatalytic activity. Among all metals, Pt/CN was found to be the best performer both under sunlight and UV-visible irradiation. Under sunlight, maximum H2@ 2.7 mmol/h/g was observed over Pt/CN followed by Pd/CN > Au/CN > Ag/CN > Cu/CN ≈ CN. The present study revealed that among all metals, Pt formed superior interfacial contact with g-C3N4 as compared to other metals. The maximum Schottky barrier height (Φb,Pt) of 0.66 V was observed at Pt/CN followed by Φb,Au/CN (0.46 V) and Φb,Pd/CN (0.05 V). The presence of electron-deficient Pt in Pt-XPS, decrease in the intensity of d-DOS of Pt near the Fermi level in VB-XPS, increase in CB tail states, and cathodic shift in Vfb in MS plots sufficiently confirmed strong metal-support interactions in Pt/CN. Due to the SPR effect, Au and Ag NPs suffered from agglomeration and poor dispersion during photodeposition. Finely dispersed Pt NPs (2-4 nm, 53% dispersion) successfully competed with shallow/deep trap states and drove the photogenerated electrons to active metallic sites in a drastically reduced time period as investigated by femtosecond transient absorption spectroscopy. Typically, an interfacial electron transfer rate, KIET,avg, of 2.5 × 1010 s-1 was observed for Pt/CN, while 0.087 × 1010 s-1 was observed in Au/CN. Band alignment/potentials at M/CN Schottky junctions were derived and most favorable in Pt/CN with CB tail states much above the water reduction potential; however, in the case of Pd, these extend much below the H+/H2 potential and hence behave like deep trap states. Thus, in Pd/CN (τ0 = 4200 ps, 49%) and Ag/CN (3870 ps, 53%), electron deep trapping dominates over charge transfer to active sites. The present study will help in designing futuristic new cocatalyst-photocatalyst systems.

The chromosome-scale genome assembly of cluster bean provides molecular insight into edible gum (galactomannan) biosynthesis family genes.

Cluster bean (Cyamopsis tetragonoloba (L.) Taub 2n = 14, is commonly known as Guar. Apart from being a vegetable crop, it is an abundant source of a natural hetero-polysaccharide called guar gum or galactomannan. Here, we are reporting a chromosome-scale reference genome assembly of a popular cluster bean cultivar RGC-936, by combining sequencing data from Illumina, 10X Genomics, Oxford Nanopore technologies. An initial assembly of 1580 scaffolds with an N50 value of 7.12 Mb was generated and these scaffolds were anchored to a high density SNP linkage map. Finally, a genome assembly of 550.31 Mb (94% of the estimated genome size of ~ 580 Mb (through flow cytometry) with 58 scaffolds was obtained, including 7 super scaffolds with a very high N50 value of 78.27 Mb. Phylogenetic analysis using single copy orthologs among 12 angiosperms showed that cluster bean shared a common ancestor with other legumes 80.6 MYA. No evidence of recent whole genome duplication event in cluster bean was found in our analysis. Further comparative transcriptomics analyses revealed pod-specific up-regulation of genes encoding enzymes involved in galactomannan biosynthesis. The high-quality chromosome-scale cluster bean genome assembly will facilitate understanding of the molecular basis of galactomannan biosynthesis and aid in genomics-assisted improvement of cluster bean.

Study Protocol of the Bladder Adjuvant RadioTherapy (BART) Trial: A Randomised Phase III Trial of Adjuvant Radiotherapy Following Cystectomy in Bladder Cancer.

AIMS: To assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. MATERIALS AND METHODS: The BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy - Colorectal questionnaire is recorded pre-treatment and at follow-up. ENDPOINTS AND STATISTICS: The primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life. CONCLUSION: The BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC.

Hierarchical 3D Flower-like Metal Oxides Micro/Nanostructures: Fabrication, Surface Modification, Their Crucial Role in Environmental Decontamination, Mechanistic Insights, and Future Perspectives.

Hierarchical micro/nanostructures are constructed by micro-scaled objects with nanoarchitectures belonging to an interesting class of crystalline materials that has significant applications in diverse fields. Featured with a large surface-to-volume ratio, facile mass transportation, high stability against aggregation, structurally enhanced adsorption, and catalytical performances, three dimenisional (3D) hierarchical metal oxides have been considered as versatile functional materials for waste-water treatment. Due to the ineffectiveness of traditional water purification protocols for reclamation of water, lately, the use of hierarchical metal oxides has emerged as an appealing platform for the remediation of water pollution owing to their fascinating and tailorable physiochemical properties. The present review highlights various approaches to the tunable synthesis of hierarchical structures along with their surface modification strategies to enhance their efficiencies for the removal of different noxious substances. Besides, their applications for the eradication of organic and inorganic contaminants have been discussed comprehensively with their plausible mechanistic pathways. Finally, overlooked aspects in this field as well as the major roadblocks to the implementation of these metal oxide architectures for large-scale treatment of wastewater are provided here. Moreover, the potential ways to tackle these issues are also presented which may be useful for the transformation of current water treatment technologies.

[Pharmacological importance of novel spiro derivatives against human pathogenic fungi]. / Farmakologicheskoe znachenie novykh spiro 1,4-digidropiridinov protiv patogennykh dlia cheloveka gribov.

Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. In the present study, antifungal activity of earlier synthesized spiro-1,4-dihydropyridines (1,4-DHPs) was investigated. The antifungal activity of spiro-1,4-DHPs compounds were screened against Aspergillus flavus, A. fumigatus, and Candida albicans by using Disc Diffusion and Modified Microdilution method. Among six spiro-1,4-DHPs compounds tested all of them showed stronger antifungal activity possibly through inhibiting the synthesis of chitin in cell wall against A. flavus, A. fumigatus, and C. albicans as compared to fluconazole, a standard antifungal drug. The combination of compounds showed that the synthesized compounds had synergistic, additive effects as compared to currently used drugs as an antifungal agent. These results indicated that these designed compounds were potential chitin synthase inhibitors and had excellent antimycotic activity for the treatment of fungal infections.

Review of management practices of sinogenic intracranial abscesses in children.

OBJECTIVE: This study aimed to evaluate the management practices and outcomes in children with sinogenic intracranial suppuration. METHOD: This was a retrospective cohort study in a single paediatric tertiary unit that included patients younger than 18 years with radiologically confirmed intracranial abscess, including subdural empyema and epidural or intraparenchymal abscess secondary to sinusitis. Main outcomes studied were rate of return to the operating theatre, length of hospital stay, death in less than 90 days and neurological disability at 6 months. RESULTS: A cohort of 39 consecutive patients presenting between 2000 and 2020 were eligible for inclusion. Subdural empyema was the most common intracranial complication followed by extradural abscess and intraparenchymal abscess. Mean length of hospital stay was 42 days. Sixteen patients were managed with combined ENT and neurosurgical interventions, 15 patients underwent ENT procedures alone and 4 patients had only neurosurgical drainage. Four patients initially underwent non-operative management. The rates of return to the operating theatre, neurological deficits and 90-day mortality were 19, 9 and 3, respectively, and were comparable across the 4 treatment arms. In the univariate logistic regression, only the size of an intracranial abscess was found be associated with an increased likelihood of return to the operating theatre, whereas combined ENT and neurosurgical intervention did not result in improved outcomes. CONCLUSION: Sinogenic intracranial abscesses are associated with significant morbidity and mortality. The size of an intracranial abscess has a strong association with a need for a revision surgery.