bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of electronic apex locators in comparison with intraoral radiographs in working length determination- a systematic review and meta-analysis
Authors: Kaur Gurveen , Thomas Anchu Rachel , Samson Renu Sarah , Varghese Eby , Ponraj Ratna Rachel , Nagraj Sumanth Kumbargere , Shrivastava Deepti , Algarni Hmoud Ali , Siddiqui Amna Yusuf , Alothmani Osama S. , Srivastava Kumar Chandan
Published: May 2024

Background

Successful endodontic treatment needs accurate determination of working length (WL). Electronic apex locators (EALs) were presented as an alternative to radiographic methods; and since then, they have evolved and gained popularity in the determination of WL. However, there is insufficient evidence on the post-operative pain, adequacy, and accuracy of EALs in determining WL.

Objective

The systematic review and meta-analysis aims to gather evidence regarding the effectiveness of EALs for WL determination when compared to different imaging techniques along with postoperative pain associated with WL determination, the number of radiographs taken during the procedure, the time taken, and the adverse effects.

Methods

For the review, clinical studies with cross-over and parallel-arm randomized controlled trials (RCTs) were searched in seven electronic databases, followed by cross-referencing of the selected studies and related research synthesis. Risk of bias (RoB) assessment was carried out with Cochrane's RoB tool and a random-effects model was used. The meta-analysis was performed with the RevMan software 5.4.1.

Results

Eleven eligible RCTs were incorporated into the review and eight RCTs into the meta-analysis, of which five had high RoB and the remaining six had unclear RoB. Following meta-analysis, no significant difference in postoperative pain was found among the EAL and radiograph groups (SMD 0.00, CI .29 to .28, 354 participants; P value = 0.98). Radiograph group showed better WL accuracy (SMD 0.55, CI .11 to .99, 254 participants; P value = 0.02), while the EAL group had 10% better WL adequacy (RR 1.10, CI 1.03–1.18, 573 participants; P value = 0.006).

Conclusion

We found very low-certainty evidence to support the efficacy of different types of EAL compared to radiography for the outcomes tested. We were unable to reach any conclusions about the superiority of any type of EAL. Well-planned RCTs need to be conducted by standardizing the outcomes and outcome measurement methods.
Detection of multidrug-resistant bacteria in the nasal cavities and evaluation of sinus disorders in patients undergoing Le Fort I osteotomy
Authors: Mendes Bárbara M. , Bortoli Évelin S. , Zaleski Catherine B. , Martinelli Maila P. D. , Pascoal Vanessa F. , Oliveira Sílvia D.
Published: May 2024

Introduction

Orthognathic surgery can lead to sinus alterations, including sinusitis, attributed to the exposure of maxillary sinuses during Le Fort I osteotomy. Furthermore, being a hospital-based procedure, there is potential risk of complications arising from bacteria prevalent in such environments. This study evaluated maxillary sinusitis occurrence and the presence of multidrug-resistant bacteria in the nasal cavity before and after orthognathic surgery.

Methods

Ten patients with dentofacial deformities underwent Le Fort I osteotomy. Clinical evaluations using SNOT-22 questionnaire were performed, and nasal cavity samples were collected pre-surgery and 3–6 months post-surgery to quantify total mesophilic bacteria and detect Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumoniae. Cone Beam Computed Tomography (CBCT) was performed pre- and post-operatively, and the results were evaluated using the Lund-Mackay system. This study was registered and approved by the Research Ethics Committee of PUCRS (No. 4.683.066).

Results

The evaluation of SNOT-22 revealed that five patients showed an improvement in symptoms, while two remained in the same range of interpretation. One patient developed post-operative maxillary sinusitis, which was not detected at the time of evaluation by SNOT-22 or CBCT. CBCT showed a worsening sinus condition in three patients, two of whom had a significant increase in total bacteria count in their nasal cavities. The Brodsky scale was used to assess hypertrophy in palatine tonsils, where 60% of the subjects had grade 1 tonsils, 20% had grade 2 and 20% had grade 3. None of the patients had grade 4 tonsils, which would indicate more than 75% obstruction. Two patients harboured S. aureus and K. pneumoniae in their nasal cavities. Notably, K. pneumoniae, which was multidrug-resistant, was present in the nasal cavity of patients even before surgery, but this did not result in maxillary sinusitis, likely due to the patients’ young and healthy condition.

Conclusion

There was an improvement in signs and symptoms of maxillary sinusitis and quality of life in most patients after orthognathic surgery. However, some patients may still harbour multidrug-resistant bacteria, even if they are asymptomatic. Therefore, a thorough pre-operative assessment is essential to avoid difficult-to-treat post-operative complications.
Perioperative management of a patient with unexpectedly detected early-stage ovarian mucinous carcinoma combined with progressive bulbar paralysis: a case report and literature review
Authors: Zhang Dingbei , Xu Ruibo , Huo Tingting , Liu Ying , Hao Zengfang , Sun Yao , Xi Xiaoyu , Du Xiaoli , Wang Lili , Du Jiexian
Published: May 2024

Background

Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases.

Case presentation

In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml.

Conclusions

GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.
Evaluating anthelmintic, anti-platelet, and anti-coagulant activities, and identifying the bioactive phytochemicals of Amaranthus blitum L.
Authors: Abdel-Moez Ghada , Sayed Hanaa , Khalifa Azza , Abd-Elrahman Salwa , Osman Mohammed , Mohamed Shaymaa
Published: May 2024

Background

Highlighting affordable alternative crops that are rich in bioactive phytoconstituents is essential for advancing nutrition and ensuring food security. Amaranthus blitum L. (AB) stands out as one such crop with a traditional history of being used to treat intestinal disorders, roundworm infections, and hemorrhage. This study aimed to evaluate the anthelmintic and hematologic activities across various extracts of AB and investigate the phytoconstituents responsible for these activities.

Methods

In vitro anthelmintic activity against Trichinella spiralis was evaluated in terms of larval viability reduction. The anti-platelet activities were assessed based on the inhibitory effect against induced platelet aggregation. Further, effects on the extrinsic pathway, the intrinsic pathway, and the ultimate common stage of blood coagulation, were monitored through measuring blood coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT), respectively. The structures of isolated compounds were elucidated by spectroscopic analysis.

Results

Interestingly, a previously undescribed compound (19), N-(cis-p-coumaroyl)-ʟ-tryptophan, was isolated and identified along with 21 known compounds. Significant in vitro larvicidal activities were demonstrated by the investigated AB extracts at 1 mg/mL. Among tested compounds, compound 18 (rutin) displayed the highest larvicidal activity. Moreover, compounds 19 and 20 (N-(trans-p-coumaroyl)-ʟ-tryptophan) induced complete larval death within 48 h. The crude extract exhibited the minimal platelet aggregation of 43.42 ± 11.69%, compared with 76.22 ± 14.34% in the control plasma. Additionally, the crude extract and two compounds 19 and 20 significantly inhibited the extrinsic coagulation pathway.

Conclusions

These findings extend awareness about the nutritional value of AB as a food, with thrombosis-preventing capabilities and introducing a promising source for new anthelmintic and anticoagulant agents.
The burden of health expenditure on household impoverishment in Ethiopia: a systematic review and meta-analysis
Authors: Tsega Yawkal , Endawkie Abel , Kebede Shimels Derso , Kebede Natnael , Mihiretu Mengistu Mera , Bekele Ermias , Ayele Kokeb , Asmare Lakew , Bayou Fekade Demeke , Arefaynie Mastewal
Published: May 2024

Background

Ethiopia, like many low-income countries, faces significant challenges in providing accessible and affordable healthcare to its population. Health expenditure is a critical factor in determining the quality and accessibility of healthcare. However, high health expenditure can also have detrimental effects on households, potentially leading to impoverishment. To the best knowledge of investigators, no similar study has been conducted in Ethiopia. Therefore, this systematic review and meta-analysis aimed to determine the pooled burden of health expenditure on household impoverishment in Ethiopia.

Methods

This systematic review and meta-analysis used the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Cochrane Library, HINARI, Google Scholar and Epistemonikos electronic databases were searched systematically. Moreover, direct manual searching through google was conducted. The analysis was performed using STATA version 17 software. Heterogeneity and publication bias were assessed using I2 statistics and Egger’s test, respectively. The trim and fill method was also performed to adjust the pooled estimate. Forest plots were used to present the pooled incidence with a 95% confidence interval of meta-analysis using the random effect model.

Results

This systematic review and meta-analysis included a total of 12 studies with a sample size of 66344 participants. The pooled incidence of impoverishment, among households, attributed to health expenditure in Ethiopia was 5.20% (95% CI: 4.30%, 6.20%). Moreover, there was significant heterogeneity between the studies (I2 = 98.25%, P = 0.000). As a result, a random effect model was employed.

Conclusion

The pooled incidence of impoverishment of households attributed to their health expenditure in Ethiopia was higher than the incidence of impoverishment reported by the world health organization in 2023.
Comprehensive characterization of stemness-related lncRNAs in triple-negative breast cancer identified a novel prognostic signature related to treatment outcomes, immune landscape analysis and therapeutic guidance: a silico analysis with in vivo experiments
Authors: Zhang Min , Zhang Fangxu , Wang Jianfeng , Liang Qian , Zhou Weibing , Liu Jian
Published: May 2024

Background

Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are known to play a crucial role in the growth, migration, recurrence, and drug resistance of tumor cells, particularly in triple-negative breast cancer (TNBC). This study aims to investigate stemness-related lncRNAs (SRlncRNAs) as potential prognostic indicators for TNBC patients.

Methods

Utilizing RNA sequencing data and corresponding clinical information from the TCGA database, and employing Weighted Gene Co-expression Network Analysis (WGCNA) on TNBC mRNAsi sourced from an online database, stemness-related genes (SRGs) and SRlncRNAs were identified. A prognostic model was developed using univariate Cox and LASSO-Cox analysis based on SRlncRNAs. The performance of the model was evaluated using Kaplan–Meier analysis, ROC curves, and ROC-AUC. Additionally, the study delved into the underlying signaling pathways and immune status associated with the divergent prognoses of TNBC patients.

Results

The research identified a signature of six SRlncRNAs (AC245100.6, LINC02511, AC092431.1, FRGCA, EMSLR, and MIR193BHG) for TNBC. Risk scores derived from this signature were found to correlate with the abundance of plasma cells. Furthermore, the nominated chemotherapy drugs for TNBC exhibited considerable variability between different risk score groups. RT-qPCR validation confirmed abnormal expression patterns of these SRlncRNAs in TNBC stem cells, affirming the potential of the SRlncRNAs signature as a prognostic biomarker.

Conclusion

The identified signature not only demonstrates predictive power in terms of patient outcomes but also provides insights into the underlying biology, signaling pathways, and immune status associated with TNBC prognosis. The findings suggest the possibility of guiding personalized treatments, including immune checkpoint gene therapy and chemotherapy strategies, based on the risk scores derived from the SRlncRNA signature. Overall, this research contributes valuable knowledge towards advancing precision medicine in the context of TNBC.
Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study
Authors: Gao Weize , Peng Chong , Wang Zhan , Li Yongxin , Liu Mingjun
Published: May 2024

Background

The intricate etiology of autoimmune liver disease (AILD) involves genetic, environmental, and other factors that yet to be completely elucidated. This study comprehensively assessed the causal association between genetically predicted modifiable risk factors and AILD by employing Mendelian randomization.

Methods

Genetic variants associated with 29 exposure factors were obtained from genome-wide association studies (GWAS). Genetic association data with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also obtained from publicly available GWAS. Univariate and multivariate Mendelian randomization analyses were performed to identify potential risk factors for AILD.

Results

Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, 95%CI 1.423–1.843, P = 2.506 × 10− 13) was significantly associated with an increased risk of AIH. Genetically predicted smoking initiation (OR = 1.637, 95%CI 1.055–2.540, P = 0.028), lower coffee intake (OR = 0.359, 95%CI 0.131–0.985, P = 0.047), cholelithiasis (OR = 1.134, 95%CI 1.023–1.257, P = 0.017) and higher C-reactive protein (CRP) (OR = 1.397, 95%CI 1.094–1.784, P = 0.007) were suggestively associated with an increased risk of AIH. Genetically predicted inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127–1.303, P = 2.015 × 10− 7) and RA (OR = 1.417, 95%CI 1.193–1.683, P = 7.193 × 10− 5) were significantly associated with increased risk of PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI 1.005–1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1.086, 95%CI 1.017–1.160, P = 0.014) and higher CRP (OR = 1.199, 95%CI 1.019–1.410, P = 0.028) were suggestively associated with an increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560–0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699–0.995, P = 0.044) levels were suggestive protective factors for PBC. Genetically predicted smoking initiation (OR = 0.630, 95%CI 0.462–0.860, P = 0.004) was suggestively associated with a decreased risk of PSC. Genetically predicted IBD (OR = 1.252, 95%CI 1.164–1.346, P = 1.394 × 10− 9), RA (OR = 1.543, 95%CI 1.279–1.861, P = 5.728 × 10− 6) and lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141–0.510, P = 6.172 × 10− 5) were positively associated with an increased risk of PSC.

Conclusions

Evidence on the causal relationship between 29 genetically predicted modifiable risk factors and the risk of AIH, PBC, and PSC is provided by this study. These findings provide fresh perspectives on the management and prevention strategies for AILD.
ESKEMAP: exact sketch-based read mapping
Authors: Schulz Tizian , Medvedev Paul
Published: May 2024

Background

Given a sequencing read, the broad goal of read mapping is to find the location(s) in the reference genome that have a “similar sequence”. Traditionally, “similar sequence” was defined as having a high alignment score and read mappers were viewed as heuristic solutions to this well-defined problem. For sketch-based mappers, however, there has not been a problem formulation to capture what problem an exact sketch-based mapping algorithm should solve. Moreover, there is no sketch-based method that can find all possible mapping positions for a read above a certain score threshold.

Results

In this paper, we formulate the problem of read mapping at the level of sequence sketches. We give an exact dynamic programming algorithm that finds all hits above a given similarity threshold. It runs in $$\mathcal {O} (|t| + |p| + \ell ^2)$$

O
(
|
t
|
+
|
p
|
+

ℓ
2

)

time and $$\mathcal {O} (\ell \log \ell )$$

O
(
ℓ
log
ℓ
)

space, where |t| is the number of $$k$$
k
-mers inside the sketch of the reference, |p| is the number of $$k$$
k
-mers inside the read’s sketch and $$\ell$$
ℓ
is the number of times that $$k$$
k
-mers from the pattern sketch occur in the sketch of the text. We evaluate our algorithm’s performance in mapping long reads to the T2T assembly of human chromosome Y, where ampliconic regions make it desirable to find all good mapping positions. For an equivalent level of precision as minimap2, the recall of our algorithm is 0.88, compared to only 0.76 of minimap2.
Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery
Authors: Zhang TianHong , Wei YanYan , Tang XiaoChen , Cui HuiRu , Xu LiHua , Hu YeGang , Tang YingYing , Hu Qiang , Liu HaiChun , Wang ZiXuan , Chen Tao , Li ChunBo , Wang JiJun
Published: May 2024

Background

The effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults.

Methods

A total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP−). Therefore, the four groups were defined as Adolescent-AP−, Adolescent-AP+, Adult-AP−, and Adult-AP+.

Results

During the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP− group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP− group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP− group. The Adolescent-AP− group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults.

Conclusions

Early use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.
Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer
Authors: Lautert-Dutra William , M. Melo Camila , Chaves Luiz P. , Crozier Cheryl , P. Saggioro Fabiano , B. dos Reis Rodolfo , Bayani Jane , Bonatto Sandro L. , Squire Jeremy A.
Published: May 2024

Background

In prostate cancer (PCa), well-established biomarkers such as MSI status, TMB high, and PDL1 expression serve as reliable indicators for favorable responses to immunotherapy. Recent studies have suggested a potential association between CDK12 mutations and immunotherapy response; however, the precise mechanisms through which CDK12 mutation may influence immune response remain unclear. A plausible explanation for immune evasion in this subset of CDK12-mutated PCa may be reduced MHC expression.

Results

Using genomic data of CDK12-mutated PCa from 48 primary and 10 metastatic public domain samples and a retrospective cohort of 53 low-intermediate risk primary PCa, we investigated how variation in the expression of the MHC genes affected associated downstream pathways. We classified the patients based on gene expression quartiles of MHC-related genes and categorized the tumors into “High” and “Low” expression levels. CDK12-mutated tumors with higher MHC-expressed pathways were associated with the immune system and elevated PD-L1, IDO1, and TIM3 expression. Consistent with an inflamed tumor microenvironment (TME) phenotype, digital cytometric analyses identified increased CD8 + T cells, B cells, γδ T cells, and M1 Macrophages in this group. In contrast, CDK12-mutated tumors with lower MHC expression exhibited features consistent with an immune cold TME phenotype and immunoediting. Significantly, low MHC expression was also associated with chromosome 6 loss of heterozygosity (LOH) affecting the entire HLA gene cluster. These LOH events were observed in both major clonal and minor subclonal populations of tumor cells. In our retrospective study of 53 primary PCa cases from this Institute, we found a 4% (2/53) prevalence of CDK12 mutations, with the confirmation of this defect in one tumor through Sanger sequencing. In keeping with our analysis of public domain data this tumor exhibited low MHC expression at the RNA level. More extensive studies will be required to determine whether reduced HLA expression is generally associated with primary tumors or is a specific feature of CDK12 mutated PCa.

Conclusions

These data show that analysis of CDK12 alteration, in the context of MHC expression levels, and LOH status may offer improved predictive value for outcomes in this potentially actionable genomic subgroup of PCa. In addition, these findings highlight the need to explore novel therapeutic strategies to enhance MHC expression in CDK12-defective PCa to improve immunotherapy responses.
NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells
Authors: Liu Cassie , Vorderbruggen Makenzie , Muñoz-Trujillo Catalina , Kim Sung Hoon , Katzenellenbogen John A. , Katzenellenbogen Benita S. , Karpf Adam R.
Published: May 2024

Background

Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models.

Results

We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors. Based on drug potency, efficacy, and selectivity, determined through cell viability assays, we focused on two compounds, NB-73 and NB-115 (NB compounds), for further investigation. NB compounds potently and selectively inhibited FOXM1 with lesser effects on other FOX family members. NB compounds decreased FOXM1 expression via targeting the FOXM1 protein by promoting its proteasome-mediated degradation, and effectively suppressed FOXM1 gene targets at both the protein and mRNA level. At the cellular level, NB compounds promoted apoptotic cell death. Importantly, while inhibition of apoptosis using a pan-caspase inhibitor rescued HGSOC cells from NB compound-induced cell death, it did not rescue FOXM1 protein degradation, supporting that FOXM1 protein loss from NB compound treatment is specific and not a general consequence of cytotoxicity. Drug washout studies indicated that FOXM1 reduction was retained for at least 72 h post-treatment, suggesting that NB compounds exhibit long-lasting effects in HGSOC cells. NB compounds effectively suppressed both two-dimensional and three-dimensional HGSOC cell colony formation at sub-micromolar concentrations. Finally, NB compounds exhibited synergistic activity with carboplatin in HGSOC cells.

Conclusions

NB compounds are potent, selective, and efficacious inhibitors of FOXM1 in HGSOC cells and are worthy of further investigation as HGSOC therapeutics.
Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination–deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial
Authors: Belotte Jimmy , Felicetti Brunella , Baines Amanda J. , YoussefAgha Ahmed , Rojas-Espaillat Luis , Ortiz Ana Godoy , Provencher Diane , Vázquez Raúl Márquez , Cortijo Lucia González , Zeng Xing
Published: May 2024

Background

Maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib’s efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination–deficient tumors.

Methods

OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator’s discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator’s discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination–deficient. The primary endpoint is the pre–interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1.

Discussion

OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination–deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery.

Trial registration

ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.
Production of highly cytotoxic and low immunogenic L-asparaginase from Stenotrophomonas maltophilia EMCC2297
Authors: Abdelrazek Nada A. , Saleh Sarra E. , Raafat Marwa M. , Ali Amal E. , Aboulwafa Mohammad M.
Published: May 2024

L-asparaginase is an important therapeutic enzyme that is frequently utilized in the chemotherapy regimens of adults as well as pediatric patients with acute lymphoblastic leukemia. However, a high rate of hypersensitivity with prolonged use has limited its utilization. Stenotrophomonas maltophilia (S. maltophilia) EMCC2297 isolate was reported as a novel and promising source for L- asparaginase. The present study aimed at the production, purification, and characterization of L- asparaginase from S. maltophilia EMCC2297 isolate. The microbial production of L-asparaginase by the test isolate could be increased by pre-exposure to chloramphenicol at 200 µg/ml concentration. S. maltophilia EMCC2297 L-asparaginase could be purified to homogeneity by ammonium sulphate precipitation and the purified form obtained by gel exclusion chromatography showed total activity of 96.4375 IU/ml and specific activity of 36.251 IU/mg protein. SDS-PAGE analysis revealed that the purified form of the enzyme is separated at an apparent molecular weight of 17 KDa. Michaelis-Menten constant analysis showed a Km value of 4.16 × 10− 2 M with L-asparagine as substrate and Vmax of 10.67 IU/ml. The antitumor activity of the purified enzyme was evaluated on different cell lines and revealed low IC50 of 2.2 IU/ml and 2.83 IU/ml for Hepatocellular cancer cell line (HepG-2), human leukemia cancer cell line (K-562), respectively whereas no cytotoxic effect could be detected on normal human lung fibroblast cells (MRC-5). However, mice treated with native L-asparaginase showed lower IgG titre compared to commercial L-asparaginase. This study highlights the promising characteristics of this enzyme making it a valuable candidate for further research and development to be an adduct in cancer chemotherapy.
Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii
Authors: Eltokhy Mohamed A. , Saad Bishoy T. , Eltayeb Wafaa N. , Alshahrani Mohammad Y. , Radwan Sahar M R , Aboshanab Khaled M. , Ashour Mohamed S. E.
Published: May 2024

Multidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.
First reported case in an Irish flock of MCF- like systemic necrotizing vasculitis in sheep associated with ovine herpesvirus 2
Authors: Sheehan Maresa , Pesavento Patricia A. , Campion Francis , Lynch John , McGettrick Shane , Toland Brian , Kennedy Aideen
Published: May 2024

Background

Ovine gammaherpesvirus 2 (OvHV-2) is the causative agent of sheep associated malignant catarrhal fever (MCF). As sheep are the adapted host for OvHV-2, it is generally presumed that infection is not associated with disease in this species. However, a recent case review combined in-situ hybridisation, PCR and histopathology and correlated the viral distribution with systemic necrotizing vasculitis and concluded OvHV-2 was the likely agent responsible for sporadic, MCF-like vascular disease in sheep.

Case presentation

Using similar methods this case study reports on the findings of the first reported cases in an Irish Flock of MCF- like systemic necrotizing vasculitis in sheep associated with OvHV-2. Sheep A, a 16-month-old Texel-cross hogget displayed signs of ill- thrift, Sheep B, a nine-month-old Belclare-cross lamb, was found dead having displayed no obvious symptoms. Both cases occurred on the same farm, however the animals were not related. Lymphohistiocytic vasculitis of various tissues was the predominant histopathological finding in both animals.

Conclusion

By combining histopathology, PCR and in-situ hybridisation results, MCF- like systemic necrotizing vasculitis associated with OvHV-2 has been diagnosed for the first time in an Irish flock.
Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge
Authors: Ni Jintao , Ye Danyan , Zeng Weiping , Ma Siyi , Wang Zhixia , Kuang Yuping , Yang Lujun
Published: May 2024

Background

This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model.

Methods

CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter.

Results

Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth.

Conclusion

GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.
Enhancement of work place comfort through the use of soft landscape
Authors: Ale Taiwo Ayomide , Ayeni Dorcas Aina , Adedayo Olatunde Folaranmi
Published: May 2024

The work environment has been shown to have a great influence on employees’ physical and mental state, as such employers try as much as possible to provide a comfortable working environment. However, recent studies have shown that the work environment is no longer as comfortable as it used to be due to heat gain from the increasing use of hard landscape features and neglect of soft landscape features in the work environment. This has resulted in stress causing both mild and severe health conditions for employees. Thus, this study aims to analyze the use of soft landscape in enhancing users' comfort with the view of reducing stress and health-related issues in the work environment. The paper adopted a mixed method using observation checklists, structured interviews, questionnaires, and case studies. A total of eighteen office complexes were selected to describe the existing situation as related to most office complexes and to also gain insight into the subject matter as already applied to life situations. Structured interviews and questionnaires were also conducted with occupants of the buildings and professionals to hear their perceptions and expectations of their work environment. Results showed that 20 percent of the offices give proper consideration to the use of soft landscapes in the work environment, and 40 percent give inconsiderable attention to soft landscapes while making use of them in small quantities solely for improving the aesthetical value of the building. In comparison, the remaining 40 percent do not consider landscape use as a means of improving comfort in the work environment. Findings also revealed that 80 percent of office buildings give major consideration to parking space using hard landscapes without a proper blend of soft landscapes after building design which hurts occupant comfort. The research concluded that the incorporation of soft landscape elements both within the building using recesses and protrusions and on the building walls through the use of exoskeleton and climbers while incorporating trees, shrubs, flowers, hedges and water around the building can have these required effects on employee’s comfort.
Non-infectious respiratory complications after allogeneic bone marrow transplantation: single center experience in Egypt
Authors: Motawea Mona M. , Samra Mohamed Abd Elmooti , Ganna Salwa Atef , Elshafey Basem Ibrahim
Published: May 2024

Background

Hematopoietic progenitor cells are infused intravenously, known as hematopoietic stem cell transplantation. The range of pulmonary problems after transplantation of hematopoietic stem cells varies significantly from infectious to non-infectious aetiologies.

Objectives

To study noninfectious respiratory complications in patients subjected to allogeneic bone marrow transplants.

Patients and methods

This retrospective study was carried out on 1000 patients with hematopoietic stem-cell transplantations. These patients were presented with respiratory symptoms suggestive of pulmonary complications following bone marrow transplant.

Result

The number of patients in this period was 1000 patients, and 247 of them had non-infectious pulmonary complications. Number and percent of bronchiolitis obliterans, diffuse alveolar hemorrhage, graft-versus-host disease (GVHD), pulmonary edema, Bronchiolitis obliterans with GVHD, Chemotherapy pneumonitis, Idiopathic pneumonia syndrome and Thoracic air leak syndrome to all number of cases were twenty-five (2.5%), sixteen (1.6%), eighty-one (8.1) sixty-four (25.9%), nineteen (1.9%), twenty-one (2.1%), thirteen (1.3%) and eight (0.8%) respectively, but number and percent of bronchiolitis obliterans, diffuse alveolar hemorrhage, GVHD, pulmonary edema, bronchiolitis obliterans with GVHD, chemotherapy-associated pneumonitis, Idiopathic pneumonia syndrome, and thoracic air leak syndrome to all complicated cases only were twenty-five (10.1%), sixteen (6.5%), eighty-one (32.8%), sixty-four (25.9 %), nineteen (7.7%), twenty-one (8.5 %), thirteen (5.3 %) and eight (3.2%) respectively.

Conclusions

Noninfectious respiratory complications included GVHD, pulmonary edema, bronchiolitis obliterans and diffuse alveolar hemorrhage bronchiolitis obliterans with GVHD, chemotherapy-associated pneumonitis, Idiopathic pneumonia syndrome, and thoracic air leak syndrome. Some of them occurred early, and some occurred late. The incidence of non-infectious respiratory complications is affected by increased patient age and female gender.
Associations of Plasma and Fecal Metabolites with Body Mass Index and Body Fat Distribution in Children
Authors: Hong Zhen , Zhou Kejun , Wei Yuanhuan , Ma Bingjie , Xie Guoxiang , Zhang Zheqing , Liang Jingjing
Published: May 2024

Context

Childhood obesity continues to be a critical public health concern with far-reaching implications for well-being.

Objective

This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6 to 9 years in China.

Methods

This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies.

Results

A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry. By using orthogonal projections to latent structures discriminant analysis and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (β −1.373 to −.016, pFDR < 0.001-0.031; β −1.008 to −.071, pFDR 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (β .023-2.396, pFDR < 0.001; β .014-1.736, pFDR < 0.001-0.049).

Conclusion

Plasma and fecal metabolites such as glutamine may serve as potential therapeutic targets for the development of obesity.
N-terminal Pro-B-Type Natriuretic Peptide and Risk for Diabetes Mellitus and Metabolic Syndrome
Authors: Nicoli Charles D , Long D Leann , Plante Timothy B , Judd Suzanne E , McClure Leslie A , Carson April P , Cushman Mary
Published: May 2024

Context

Natriuretic peptide concentrations are inversely associated with risk of diabetes mellitus and may be protective from metabolic dysfunction.

Objective

We studied associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes, metabolic syndrome (MetS), and MetS components.

Methods

A total of 2899 participants with baseline (2003-2007) and follow-up (2013-2016) examinations and baseline NT-proBNP measurement in the REasons for Geographic And Racial Differences in Stroke study. Logistic regression models were fitted to incident MetS, MetS components, and diabetes; covariates included demographics, risk and laboratory factors. Incident diabetes was defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of insulin or hypoglycemic drugs at follow-up but not baseline. Incident MetS was defined as participants with ≥3 harmonized criteria at follow-up and <3 at baseline.

Results

A total of 310 participants (2364 at risk) developed diabetes and 361 (2059 at risk) developed MetS over a mean 9.4 years of follow-up. NT-proBNP was inversely associated with odds of incident diabetes (fully adjusted OR per SD higher log NT-proBNP 0.80, 95% CI 0.69-0.93) and MetS in the highest vs lowest quartile only (fully adjusted OR 0.59, 95% CI 0.37-0.92); the linear association with incident MetS was not statistically significant. NT-proBNP was inversely associated with incident dysglycemia in all models (fully adjusted OR per SD log NT-proBNP 0.65, 95% CI 0.53-0.79), but not with other MetS components. Effect modification by sex, race, age, or body mass index was not observed.

Conclusion

NT-proBNP was inversely associated with odds of diabetes, MetS, and the MetS dysglycemia component. The metabolic implications of B-type natriuretic peptides appear important for glycemic homeostasis.
Residual Axillary Metastases in Node-Positive Breast Cancer Patients After Neoadjuvant Treatment: A Register-Based Study
Authors: Munck Frederikke , Jensen Maj-Britt , Vejborg Ilse , Gerlach Maria K. , Maraldo Maja V. , Kroman Niels T. , Tvedskov Tove H. F.
Published: May 2024

Background

Lymph node (LN) metastasis after neoadjuvant chemotherapy (NACT) generally warrants axillary lymph node dissection, which opposes guidelines of upfront surgery in many cases. We investigated the risk of having additional metastases in the axilla when the LNs removed by targeted axillary dissection (TAD) harbored metastases after NACT. We aimed to identify subgroups suitable for de-escalated axillary treatment.

Methods

This register-based study used data from the Danish Breast Cancer Cooperative Group database. Data were analyzed with logistic regression models. The primary outcome was the metastatic burden in non-TAD LNs in patients with positive TAD LNs after NACT.

Results

Among 383 patients, < 66.6% positive TAD LNs (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17–0.62), only isolated tumor cells (ITCs) [OR 0.11, 95% CI < 0.01–0.82], and breast pathological complete response (pCR) [OR 0.07, 95% CI < 0.01–0.56] were associated with a low risk of having more than three positive non-TAD LNs. In 315 patients with fewer than three positive non-TAD LNs, the proportion of positive TAD LNs (OR 0.45, 95% CI 0.27–0.76 for 33.3–66.6% vs. > 66.6%), size of the TAD LN metastasis (OR 0.14, 95% CI 0.04–0.54 for ITC vs. macrometastasis), tumor size at diagnosis (OR 0.30, 95% CI 0.15–0.64 for 20–49 mm vs. ≥ 50 mm) and breast pCR (OR 0.38, 95% CI 0.15–0.96) were associated with residual LN metastases in the axilla.

Conclusions

Breast pCR or ITC only in TAD LNs can, with reasonable certainty, preclude more than three positive non-TAD LNs. Additionally, patients with only ITCs in the TAD LN had a low risk of having any non-TAD LN metastases after NACT. De-escalated axillary treatment may be considered in both subgroups.