Group R2 Research Articles

Experimental analysis of frost resistance and failure models in engineered cementitious composites with the integration of Yellow River sand

Abstract This study investigates the potential use of Yellow River sand (YRS) sourced from the lower reaches of the Yellow River in China as a sustainable and cost-effective substitute for quartz sand in engineered cementitious composites (ECCs). This region accumulates around 400 million tons of sand annually. The study evaluates the impact of different YRS replacement percentages (0, 25, 50, 75, and 100%) on mechanical and microstructure properties under freeze-thaw conditions, focusing on assessing the ECC durability during cooling cycles. The results show that YRS exhibits a smaller normal distribution of particle sizes compared to that of quartz sand and a 5.77 times greater specific surface area, affecting the ECC particle size distribution. After 300 cooling cycles, the R25 group maintains 97.5% of the initial mass and 79.4% of flexural strength, indicating superior durability. The R25 group also demonstrates a minimal decrease of 11.5% in equivalent bending strength, reaching a level of 104.4% compared to R0. The R25 group’s porosity is 30.80%, with an average pore size of 20.47 mm, showing 1.3% and 6.7% decreases compared to the R0 group. Additionally, this study establishes a failure progression equation using the Weibull probability distribution model, with calculated values closely aligning with measured values. Overall, this study recommends using YRS as a sustainable ECC material.

Structural and genetic basis for the binding of a mouse monoclonal antibody to Flavobacterium psychrophilum lipopolysaccharide.

A mouse monoclonal antibody (mAb FL100A) previously prepared against Flavobacterium psychrophilum (Fp) CSF259-93 has now been examined for binding to lipopolysaccharides (LPS) of this strain and Fp 950106-1/1. The corresponding O-polysaccharides (O-PS) of these strains are formed by identical trisaccharide repeats composed of l-Rhamnose (l-Rha), 2-acetamido-2-deoxy-l-fucose (l-FucNAc) and 2-acetamido-4-R1-2,4-dideoxy-d-quinovose (d-Qui2NAc4NR1) where R1 represents a dihydroxyhexanamido moiety. The O-PS loci of these strains are also identical except for the gene (wzy1 or wzy2) that encodes the polysaccharide polymerase. Accordingly, adjacent O-PS repeats are joined through d-Qui2NAc4NR1 and l-Rha by wzy2-dependent α(1-2) linkages in Fp CSF259-93 versus wzy1-dependent β(1-3) linkages in Fp 950106-1/1. mAb FL100A reacted strongly with Fp CSF259-93 O-PS and LPS but weakly or not at all with Fp 950106-1/1 LPS and O-PS. Importantly, it also labelled cell surface blebs on the former but not the latter strain. Additionally, mAb binding was approximately 5-times stronger to homologous Fp CSF259-93 LPS than to LPS from a strain with a different R-group gene. A conformational epitope for mAb FL100A binding was suggested from molecular dynamic simulations of each O-PS. Thus, Fp CSF259-93 O-PS formed a stable well-defined compact helix in which the R1 groups were displayed in a regular pattern on the helix exterior while unreactive Fp 950106-1/1 O-PS adopted a flexible extended linear conformation. Taken together, the findings establish the specificity of mAb FL100A for Wzy2-linked F. psychrophilum O-PS and LPS.

The effect of ethanolic extract of Moringa oleifera leaves on sperm parameters in 4G-cellphone-EMR exposed rats

Cell phone use and infertility are topics of scientific investigation. 2G, 3G and 4G cell phone radiation causes negative effects on spermatogenesis. The aim of this study is to assess the protective efficiency of Moringa oleifera leaves (MOL) on the sperm parameters of Wistar rats against electromagnetic radiation (EMR) emitted from a 4G mobile phone. Male Wistar rats were divided into five groups. Control group (n=3) without mobile phone; Sham group (n=3) with mobile phone in switched-off mode; MOL-2 group (n=6) obtained orally 200 mg ethanol extract of MOL/kg BW/two months; R2 group (n=6) subjected to 4G-EMR for 96 minutes/day/two months; R2+MOL group (n=6) treated with MOL extract while exposed to EMR for two months. After the experimental period, rats were sacrificed to get epididymises. The epididymal fluid was collected to evaluate count, viability, motility and morphology of sperms. The 4G-EMR induced a significant reduction in the count and tail defects of sperms (P<0.05) in R2 rats as compared to control, sham and MOL-2 groups. Nevertheless, MOL extract significantly inhibited the EMR-caused fall of those variables in R2+MOL group. The R2 group had significantly (P<0.0001) lower and higher values concerning the sperm’s progressive motility and non-motility rates, the percentages of alive and dead sperms than those in the control, sham, and MOL-2 groups, but the MOL extract restored the parameters in R2+MOL as compared to R2 group. The oral administration of 200 mg of ethanolic extract of Moringa leaves protected the sperm parameters of Wistar rats to near normal level from harmful effects of 4G-cell phone-EMR.

Exercise and Quality of Life (QoL) in Patients Undergoing Active Breast Cancer Treatment-Comparison of Three Modalities of a 24-Week Exercise Program-A Randomized Clinical Trial.

Exercise is an accepted intervention to improve the quality of life (QoL) of breast cancer patients. Exercise programs have been developed, and all have shown satisfactory results in improving the QoL. There is a lack of research comparing different prescription modalities. The aim of this study is to evaluate the effectiveness of physical exercise (in-person and home-based, compared to the exercise recommendation) on the QoL in breast cancer patients actively undergoing treatment. This is a randomized clinical trial with three groups (in-person: guided and supervised in-person exercise program; home-based exercise: guided and supervised exercise program with streaming monitoring both as a intervention groups; and recommendation: exercise recommendation as a control group). The QoL was measured using the EORTIC QLQ-C30 questionnaire. A baseline and 24-week analysis were investigated. The total sample analyzed was n = 80. The QoL improved significantly at 24 weeks in the face-to-face and home-based exercise groups, but not in the control group. Exercise in all modalities improved fatigue, nausea, vomiting, appetite, and constipation. The QoL at 24 weeks depended on active chemotherapy, tumor type, and assigned exercise group (r2 = 0.503; p < 0.001). The QoL in breast cancer patients undergoing active treatment improved after a 24-week exercise program, especially in face-to-face and home-based exercise. Home-based exercise and streaming-based recommendation is a viable option for exercise recommendation.

Identification of genetically plastic forms among Belarusian ancient flax (Linum usitatissimum convar. elongatum Vav. et Ell.) varieties using the Linum Insertion Sequence LIS-1

The Linum Insertion Sequence 1 (LIS-1) occurs in the genetically plastic flax genotypes in response to the lack or excess of mineral and water nutrition, but also naturally, and can be transmitted to the progeny. We have analyzed 21 ancient Belarusian varieties of flax Linum usitatissimum convar. elongatum Vav. et Ell. The LIS-1 presence or absence was checked for individual plants in at minimum two generations with primer-specific polymerase chain reaction (PCR) and agarose gel electrophoresis. The studied flax varieties formed four groups: non-responsive varieties (LIS-1 was not found, group NR); responsive, which formed and completely lost the insertion (group R0); responsive, which formed and retained LIS-1 (group R1); and responsive unstable (group R2). A statistically significant difference was found in ‘plant height’ (p &lt; 0.05), ‘technical length of the stem’ (p &lt; 0.05) between R0 and NR, and R2 and NR LIS-1 groups. The machine learning algorithm random forest classifier was used to predict the presence, absence or heterozygosity of LIS-1 in flax plants based on their growth and reproductive characteristics. As a result, the accuracy of the prediction was 98% on test data. In terms of sources for the selection of fibre flax varieties adaptive to environmental challenges, the most promising group consists of responsive varieties that have formed LIS-1 insertion (R0, R1 and R2 groups).

Impact of resection margin on outcome in soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy

BackgroundThe standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification.MethodsMedical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival.ResultsA total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67–58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07–0.7, p = 0.01). Kaplan–Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups.ConclusionsR1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.

Prognostic factors and treatment responses among patients with gross residual disease in differentiated thyroid cancer.

Various postoperative staging systems were developed to assess the outcome of differentiated thyroid cancer from initial risk after surgery to dynamic changing prognosis during follow-up. The objective of our retrospective cohort study was to identify risk factors contributing to macroscopic positive surgical margin (R2 resection) and parameters in discriminating the treatment responses and prognosis among R2 patients. In total, 242 differentiated thyroid cancer patients with extrathyroidal extension who underwent a thyroidectomy at Kaohsiung Chang Gung Memorial Hospital between January 2013 and July 2018, were included. The patients were grouped according to the presence or absence of gross residual disease (R2). The R2 patients were further classified into two categories according to their treatment response into excellent and nonexcellent groups. The parameters and treatment outcomes were compared between these groups. The mean follow-up time was 45.3 months. Two hundred seven (85.5%) patients had either surgery-free or microscopic margins (R0/R1), while 35 (14.5%) had R2 resection. In the R2 group (n = 35), 15 (42.9%) patients achieved an excellent response, while 20 (57.1%) achieved a nonexcellent response. Statistically significant differences were observed in the extent of neck dissection, TSH-Tg level, post-RAI Tg level, nodal status, and recurrence between the two groups. The Kaplan-Meier curves for 5-year local and distant recurrence-free survival of R0/R1 versus R2 patients were 90.0% versus 66.3%, and 98.4% versus 90.7%, respectively ( p < 0.001). Among the R2 patients, the excellent responders had a higher local recurrence-free survival than nonexcellent responders (93.3% vs. 45.1%, p = 0.008). There are significant disparities in recurrence-free survival among R2 patients with different treatment responses. The nodal status of papillary thyroid cancer and thyroglobulin level after thyroidectomy and RAI were factors contributing to difference in their treatment responses.

Effects and mechanisms of oxytetracycline and norfloxacin on microbial extracellular polymeric substances (EPS) in biological denitrification of aquaculture wastewater

The direct equalizing ray method was employed to design three groups of mixtures of oxytetracycline(OTC) and norfloxacin(NOR) with varying proportions(Group R1 had a higher proportion of OTC, while R2 had similar concentrations of both antibiotics, and R3 had a higher proportion of NOR).The effects of these mixtures on the content and properties of extracellular polymeric substances (EPS) in the biological denitrification process were investigated using an sequencing batch reactor activated sludge reactor (SBR). The results revealed that the removal rates of ammonia nitrogen(NH3-N) decreased in all three groups with the addition of antibiotics. As the antibiotic concentration increased, the EPS content decreased by 68.46%, 55.53%, and 65.03% in R1, R2, and R3, respectively. To understand the interaction mechanism of mixed antibiotics on EPS in activated sludge, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) techniques were employed. The findings demonstrated significant effects of mixed antibiotics on functional groups such as C-O, CO, and C-O-C. Specifically, hydrogen bonding was found to be the primary influencing factor in the R1 ratio, while Π-Π conjugation played a major role in the R3 ratio.

Appendicular Muscle Mass Index as the Most Important Determinant of Bone Mineral Content and Density in Small for Gestational Age Children.

Preterm small for gestational age (SGA) children are at increased risk for low bone mineral content later in life; however, data on SGA children born at term are scarce. We included 44 SGA and 57 adequate for gestational age (AGA) children aged 6 to 11 years to compare bone mineral density (BMD) and bone mineral content (BMC) and to identify which anthropometric and biochemical values influence bone mineralization in these children. Fat mass, appendicular skeletal muscle mass index (ASMMI), BMC, and BMD were significantly lower in SGA children than in AGA (P ≤ .005). Appendicular muscle mass index correlated with BMC(TBLH,FN,L1-L4) and BMD(TBLH,FN,L1-L4) in both groups (r2 = 0.7, P < .05). In multivariate analysis, ASMMI was strongly associated with BMC and BMD in both groups. There were no differences in clinical biomarkers, calcium intake, and physical activity between the groups. Achieving adequate muscle mass contributes to adequate bone mineralization and a lower risk for low BMC and BMD in SGA children.

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists.

The farnesoid X receptor (FXR) has been recognized as a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). FXR agonists benefit NAFLD by modulating bile acid synthesis and transport, lipid metabolism, inflammation, and fibrosis pathways. However, there are still great challenges involved in developing safe and effective FXR agonists. To investigate the critical factors contributing to their activity on the FXR, 3D-QSAR molecular modeling was applied to a series of isoxazole derivatives, using comparative molecular field analysis (CoMFA (q2 = 0.664, r2 = 0.960, r2pred = 0.872)) and comparative molecular similarity indices analysis (CoMSIA (q2 = 0.706, r2 = 0.969, r2pred = 0.866)) models, which demonstrated strong predictive ability in our study. The contour maps generated from molecular modeling showed that the presence of hydrophobicity at the R2 group and electronegativity group at the R3 group in these compounds is crucial to their agonistic activity. A molecular dynamics (MD) simulation was carried out to further understand the binding modes and interactions between the FXR and its agonists in preclinical or clinical studies. The conformational motions of loops L: H1/H2 and L: H5/H6 in FXR-ligand binding domain (LBD) were crucial to the protein stability and agonistic activity of ligands. Hydrophobic interactions were formed between residues (such as LEU287, MET290, ALA291, HIS294, and VAL297) in helix H3 and ligands. In particular, our study found that residue ARG331 participated in salt bridges, and HIS447 participated in salt bridges and hydrogen bonds with ligands; these interactions were significant to protein-ligand binding. Eight new potent FXR agonists were designed according to our results, and their activities were predicted to be better than that of the first synthetic FXR agonist, GW4064.

Ureidopenicillins Are Potent Inhibitors of Penicillin-Binding Protein 2 from Multidrug-Resistant Neisseria gonorrhoeae H041.

Effective treatment of gonorrhea is threatened by the increasing prevalence of Neisseria gonorrhoeae strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses. We found that the ureidopenicillin piperacillin has a second-order rate of acylation against PBP2 that is 12-fold higher than cefoperazone and 85-fold higher than ceftriaxone and a lower MIC against H041 than ceftriaxone. Surprisingly, the affinity of ureidopenicillins for PBP2 is minimal, indicating that their inhibitory potency is due to a higher rate of the acylation step of the reaction compared to cephalosporins. Enhanced acylation results from the combination of a penam scaffold with a 2,3-dioxopiperazine-containing R1 group. Crystal structures show that the ureido β-lactams overcome the effects of resistance mutations present in PBP2 from H041 by eliciting conformational changes that are hindered when PBP2 interacts with the weaker inhibitor ceftriaxone. Overall, our results support the potential of piperacillin as a treatment for gonorrhea and provide a framework for the future design of β-lactams with improved activity against ESC-resistant N. gonorrhoeae.

The effectiveness of Moringa oleifera in the preservation of periodontium after radiation therapy: An experimental animal study

BackgroundRadiation therapy produces reactive oxygen species, which have been linked to various degenerative conditions in periodontal attachment. This study aimed to assess the beneficial effects of aqueous Moringa oleifera leaf extract on the periodontium of albino rats exposed to fractionated gamma radiation. Materials and methodsThis experimental study involved 24 adult male albino rats divided into three groups: Group M received M. oleifera leaf extract (300 mg/kg) intraperitoneally for 14 days; Group R received 20 Gy fractionated gamma irradiation; and Group MR received the same M. oleifera regimen as Group M and then fractionated gamma irradiation dose as Group R. On the first and seventh days post-radiation, bone, cementum, and periodontal ligament samples were histologically and histomorphometrically examined. ResultsThe periodontal ligament, alveolar bone, and cementum showed structural damage in Group R. A relative persistence of normal periodontal tissue structures was seen in Group MR, showing less disruption of the periodontal ligament and greater trabecular bone thickness than Group R. The histomorphometric analysis showed that the mean periodontal ligament width was highest in Group R7 (245.20 μm) and lowest in Group M7 (54.55 μm). In addition, the mean cementum width was highest in Group R1 (88.99 μm) and lowest in Group M1R1 (17.87 μm) and differed significantly between groups. ConclusionWithin the limitations of this study, Moringa oleifera leaf aqueous extract showed the potential to reduce the adverse effects of radiation, control inflammation, and support tissue healing in a rat model.

Effect of rituximab on immune status in children with aggressive mature B-cell lymphoma/leukemia–a prospective study from CCCG-BNHL-2015

BackgroundLimited research has been conducted on the impact of rituximab on immune function and the incidence of side effects in children undergoing combination chemotherapy for aggressive mature B-cell lymphoma/leukemia. MethodsClinical data from 85 patients with primary pediatric aggressive mature B-cell lymphoma/leukemia, treated according to the Chinese Children's Cancer Group (CCCG)-mature B-cell non-Hodgkin lymphoma (BNHL)-2015 protocol from June 1, 2015, to December 1, 2022, were collected from three tertiary medical centers in China. Patients with pre-existing malignancies or primary immune deficiencies (PIDs) were excluded. ResultsBetween June 1, 2015, and December 1, 2022, 85 patients (65 [76.5%] boys and 20[23.5%] girls; mean age, 6.95 years) were enrolled, and immune data at baseline during follow-up were analyzed. At the end of chemotherapy, a higher proportion of patients in the R4 group exhibited a decrease in peripheral blood CD3− CD19+ B cells (20[100%] of 20 vs 13[47.8%] of 18, p = 0.04), CD3+ T cells (21[91.3%] of 23 vs 14[60.9%] of 23, p = 0.016), and serum IgM (14[60.9%] of 23 vs 4[17.4%] of 23, p = 0.003) compared to the R3 group. However, these differences were no longer statistically significant six months after chemotherapy administration. The combination of rituximab with AA was associated with a higher incidence of significant thrombocytopenia (49[81.7%] of 60 vs 29[52.7%] of 55, p = 0.001) and infection (35[58.3%] of 60 vs 17[30.9%] of 55, p = 0.003) compared to AA alone. Furthermore, the combination of rituximab with BB was linked to a higher incidence of significant thrombocytopenia (32[52.5%] of 61 vs 31[31.0%] of 100, p = 0.007) compared to BB alone. ConclusionsWhile the effects of rituximab in combination with intense chemotherapy for childhood aggressive mature B-cell lymphoma/leukemia on children's immune function generally recovers within six months it may still prolong the recovery from immunoglobulinemia, posing a risk of secondary infections. Further studies are required to identify children with potential primary immunodeficiencies.

Hemodynamic and neuromuscular basis of reduced exercise capacity in patients with end-stage renal disease.

The present study aimed to characterize the exercise-induced neuromuscular fatigue and its possible links with cerebral and muscular oxygen supply and utilization to provide mechanistic insights into the reduced exercise capacity characterizing patients with end-stage renal disease (ESRD). Thirteen patients with ESRD and thirteen healthy males (CTR group) performed a constant-force sustained isometric contraction at 50% of their maximal voluntary isometric contraction (MVC) until exhaustion. Quadriceps muscle activation during exercise was estimated from vastus lateralis, vastus medialis, and rectus femoris EMG. Central and peripheral fatigue were quantified via changes in pre- to postexercise quadriceps voluntary activation (ΔVA) and quadriceps twitch force (ΔQtw,pot) evoked by supramaximal electrical stimulation, respectively. To assess cerebral and muscular oxygenation, throughout exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin (∆O2Hb), deoxyhemoglobin (∆HHb), and total hemoglobin (∆THb) in the prefrontal cortex and in the vastus lateralis muscle. ESRD patients demonstrated lower exercise time to exhaustion than that of CTR (88.8 ± 15.3s and 119.9 ± 14.6s, respectively, P < 0.01). Following the exercise, MVC, Qtw,pot, and VA reduction were similar between the groups (P > 0.05). There was no significant difference in muscle oxygenation (∆O2Hb) between the two groups (P > 0.05). Cerebral and muscular blood volume (∆THb) and oxygen extraction (∆HHb) were significantly blunted in the ESRD group (P < 0.05). A significant positive correlation was observed between time to exhaustion and cerebral blood volume (∆THb) in both groups (r2 = 0.64, P < 0.01). These findings support cerebral hypoperfusion as a factor contributing to the reduction in exercise capacity characterizing ESRD patients.

A single-centre, real-world study of BTK inhibitors for the initial treatment of MYD88mut /CD79Bmut diffuse large B-cell lymphoma.

MCD (MYD88L265P /CD79Bmut ) diffuse large B-cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut . Twenty-three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab + lenalidomide (R2 ). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R-CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression-free survival (PFS) of the two groups. The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R2 . Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group. In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (p = 0.028). There were no significant differences in grade 3-4 haematological toxicity (p = 1) and grade 3-4 non-haematological toxicity (p = 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 haematologic toxicity and non-haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. The efficacy of BTKi combined with R-CHOP was similar to previous reports, which was significantly better than R-CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R-CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non-GCB, DEL or high-IPI-score DLBCL patients with MYD88mut and/or CD79Bmut . In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R-miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real-world clinical data.

Survival Comparison of Different Operation Types for Middle Bile Duct Cancer: Bile Duct Resection versus Pancreaticoduodenectomy Considering Complications and Adjuvant Treatment Effects.

Margin status is one of the most significant prognostic factors after curative surgery for middle bile duct (MBD) cancer. Bile duct resection (BDR) is commonly converted to pancreaticoduodenectomy (PD) to achieve R0 resection. Additionally, adjuvant treatment is actively performed after surgery to improve survival. However, the wider the range of surgery, the higher the chance of complications; this, in turn, makes adjuvant treatment impossible. Nevertheless, no definitive surgical strategy considers the possible complication rates and subsequent adjuvant treatment. We aimed to investigate the appropriate surgical type considering the margin status, complications, and adjuvant treatment in MBD cancer. From 2008 to 2017, 520 patients diagnosed with MBD cancer at the Samsung Medical Center were analyzed retrospectively according to the operation type, margin status, complications, and adjuvant treatment. The R1 group was defined as having a carcinoma margin. The 5-year survival rate for patients who underwent R0 and R1 resection was 54.4% and 33.3%, respectively (p = 0.131). Prognostic factors affecting the overall survival were the age, preoperative CA19-9 level, T stage, and N stage, but not the operation type, margin status, complications, or adjuvant treatment. The complication rates were 11.5% and 29.8% in the BDR and PD groups, respectively (p < 0.001). We observed no significant difference in the adjuvant treatment ratio according to complications (p = 0.675). Patients with PD who underwent R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those with BDR who underwent R1 resection after adjuvant treatment (p = 0.003). The survival outcome of patients with R1 margins who underwent BDR did not match those with R0 margins after PD, even after adjuvant treatment. Due to improvements in surgical techniques and the ability to resolve complications, surgical complications exert a marginal effect on survival. Therefore, surgeons should secure R0 margins to achieve the best survival outcomes.

Accuracy of Haematology Analyzer in the Diagnosis of Malaria in Comparison with Gold Standard Microscopy

Objective: To assess the accuracy of Haematology analyzer in the diagnosis of malaria in comparison with gold standard microscopy.&#x0D; Methodology: A cross-sectional study was conducted at the Pakistan Institute of Medical Sciences and the Pakistan Atomic Energy Commission in Islamabad, Pakistan. The study was conducted for around six months, from May 2023 to October 2023. The Mindray BC-6200 haematology analyzer was utilised to evaluate a total of 191 samples, comprising 127 samples from that were infected with malaria and 64 samples from healthy controls. When the presence of malaria parasites, identified as Plasmodium vivax and Plasmodium falciparum, was detected in dyed thick blood film, a microscopy examination was carried out as a reference. Analyse-it v4.92.3 was used to create the receiver operating characteristic (ROC) curve analysis. The agreement between BC-6200 and light microscopy was assessed using the Kappa value.&#x0D; Results: The InR by BC-6200's sensitivity and specificity for P. falciparum and P. vivax infections. The sensitivity of the InR by BC-600 for P. falciparum and P. vivax was 27.9% and 85.5%, respectively. The specificity of the InR by BC-6200 for P. vivax and P. falciparum was 82.7% and 86.5%, respectively. The infection densities in microscopy varied statistically significantly between the various InR groups (χ2 = 14.50, P &lt; 0.005).An analysis was conducted on the correlation between the cell blood count and the count of InR in both the P. vivax and P. falciparum-infected patient groups. The results showed a clear correlation between InR (P. vivax group R2 = 0.87) and ΔWBC (WBCDIFF–WBCBASO). In the Mindray BC-6200 haematology analyzer, WBCBASO represents the number of WBC counting in the BASO channel with severe membrane degradation, while WBCDIFF represents the number of WBC counting in the DIFF channel with mild lyse. The volume distribution widths of RBC, HGB, and red blood cells did not differ substantially. The reticulocyte characteristics of the P. vivax/P. falciparum patient group and control group differed significantly (P&lt;0.02), although RBC, HGB, and red blood cell volume distribution width (RDW) did not differ significantly (P &gt; 0.05). There was a significant difference (P&lt;0.02) in the PLT count between the P. vivax/P. falciparum patient groups and the control group.&#x0D; Conclusion: The results imply that malaria might be screened for in a clinical setting using the BC-6200 haematology analyzer's "InR" flag and "InR#/InR‰" parameters.

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir

AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.

Survival Dynamics in Advanced Ovarian Cancer: R2 Resection Versus No-Surgery Paths Explored.

Cytoreductive surgery is critical for optimal tumor clearance in advanced epithelial ovarian cancer (EOC). Despite best efforts, some patients may experience R2 (>1cm) resection, while others may not undergo surgery at all. We aimed to compare outcomes between advanced EOC patients undergoing R2 resection and those who had no surgery. Retrospective data from 51 patients with R2 resection were compared to 122 patients with no surgery between January 2015 and December 2019 at a UK tertiary referral centre. Progression-free survival (PFS) and overall survival (OS) were the study endpoints. Principal Component Analysis and Term Frequency - Inverse Document Frequency scores were utilized for data discrimination and prediction of R>2cm from computed tomography pre-operative reports, respectively. No statistical significance was observed, except for age (73 vs 67years in the no- surgery vs R2 group, P: .001). Principal Components explained 34% of data variances. Reasons for no surgery included age, co-morbidities, patient preference, refractory disease, patient deterioration or disease progression, and absence of measurable intra- abdominal disease). The median PFS and OS were 12 and 14months for no-surgery, vs 14 and 26months for R2 (P: .138 and P: .001, respectively). Serous histology and performance status independently predicted PFS in both no-surgery and R2 cohorts. In the no-surgery cohort, serous histology independently predicted OS, while in the R2 cohorts, both serous histology and adjuvant chemotherapy were independent prognostic features for OS. The bi-grams "abdominopelvic ascites" and "solid omental" were amongst those best discriminating between R>2cm and R1-2cm. R2 resection and no-surgery cohorts displayed unfavourable prognosis with a notable degree of uniformity. When cytoreduction results in suboptimal results, the survival benefit may still be higher compared to those who underwent no surgery.

Efficient and regioselective synthesis of ortho-diiodinated homobenzylic alcohol derivatives: in silico evaluation as potential anticancer IDO/TDO inhibitors.

A simple and direct synthesis of 2,6-diiodophenylethanol building blocks through highly regioselective metalation (MIE)/oxirane SN2-type ring opening of 1,2,3-triiodobenzene is described. A significant impact of the nature of the R1 group on the reactivity of the reaction was discovered but not in terms of site-selectivity. The MIE quenching step is easily controlled by the use of slow-reacting electrophiles "oxiranes" providing solely the ortho-diiodinated homobenzylic alcohol derivatives (internal products) in excellent site-selectivity and with stereoretention. The reaction proceeded without any additives to activate the oxiranes and tolerated a wide range of substrates. The reaction of electron-deficient 1,2,3-triiodoarene systems and neutral oxiranes under the optimized conditions provided the highest isolated yields. The reaction is facile, scalable, efficient, general in scope, and generates handy precursors for further chemical manipulation. In silico interaction analysis revealed that compounds 7a, 7p, 7t and 7z established favourable interactions with the receptors IDO and TDO. Moreover, the molecular simulation results revealed stable dynamics, minimal internal fluctuations, tighter packing and more favourable dynamic features. Furthermore, the 7a-IDO reported a TBE of -26.22 ± 0.24 kcal mol-1, 7t-TDO reported a TBE of -46.66 ± 0.27 kcal mol-1, 7p-TDO reported a TBE of -48.02 ± 0.29 kcal mol-1 while 7z-TDO reported a TBE of -48.51 ± 0.28 kcal mol-1. This shows that these compounds potentially interact with IDO and TDO and consequently cause the inhibition of these targets. Moreover, the BFE results also revealed that this combination suggests that the gas-phase interactions between the components are favorable, but the solvation of the system is unfavorable. In the context of binding, it further means that the protein and ligand have attractive forces when in close proximity as seen in the gas phase, but when solvated, the system experiences an increase in free energy due to interactions with the solvent. This further implies that the binding might be enthalpically favorable due to favorable gas-phase interactions but entropically unfavorable due to unfavorable solvation effects. Our analysis shows that our designed compounds have unmatched pharmacological potential, far surpassing previously reported compounds. This highlights the innovative nature of these derivatives and sets a new benchmark in IDO and TDO drug discovery, indicating their significant potential as effective anticancer inhibitors.