bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results
Authors: Jaeger Ulrich , Worel Nina , McGuirk Joseph P. , Riedell Peter A. , Fleury Isabelle , Du Yan , Han Xia , Pearson David , Redondo Santiago , Waller Edmund K.
Published: August 2022

Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or –1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).
Human acute leukemia uses branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function
Authors: Kikushige Yoshikane , Miyamoto Toshihiro , Kochi Yu , Semba Yuichiro , Ohishi Maki , Irifune Hidetoshi , Hatakeyama Kiwamu , Kunisaki Yuya , Sugio Takeshi , Sakoda Teppei , Miyawaki Kohta , Kato Koji , Soga Tomoyoshi , Akashi Koichi
Published: August 2022

Cancer-specific metabolic activities play a crucial role in the pathogenesis of human malignancies. To investigate human acute leukemia–specific metabolic properties, we comprehensively measured the cellular metabolites within the CD34+ fraction of normal hematopoietic stem progenitor cells (HSPCs), primary human acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) cells. Here, we show that human leukemia cells are addicted to the branched-chain amino acid (BCAA) metabolism to maintain their stemness, irrespective of myeloid or lymphoid types. Human primary acute leukemias had BCAA transporters for BCAA uptake, cellular BCAA, α-ketoglutarate (α-KG), and cytoplasmic BCAA transaminase-1 (BCAT1) at significantly higher levels than control HSPCs. Isotope-tracing experiments showed that in primary leukemia cells, BCAT1 actively catabolizes BCAA using α-KG into branched-chain α-ketoacids, whose metabolic processes provide leukemia cells with critical substrates for the trichloroacetic acid cycle and the synthesis of nonessential amino acids, both of which reproduce α-KG to maintain its cellular level. In xenogeneic transplantation experiments, deprivation of BCAA from daily diet strongly inhibited expansion, engraftment and self-renewal of human acute leukemia cells. Inhibition of BCAA catabolism in primary AML or ALL cells specifically inactivates the function of the polycomb repressive complex 2, an epigenetic regulator for stem cell signatures, by inhibiting the transcription of PRC components, such as zeste homolog 2 and embryonic ectoderm development. Accordingly, BCAA catabolism plays an important role in the maintenance of stemness in primary human AML and ALL, and molecules related to the BCAA metabolism pathway should be critical targets for acute leukemia treatment.
Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia
Authors: Ilich Anton , Gernsheimer Terry B. , Triulzi Darrell J. , Herren Heather , Brown Siobhan P. , Holle Lori A. , Lucas Andrew T. , de Laat Bas , El Kassar Nahed , Wolberg Alisa S. , May Susanne , Key Nigel S.
Published: August 2022

The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)–challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 μg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, −0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.
Hepatopancreas transcriptome analyses provide new insights into the molecular regulatory mechanism of fast ovary maturation in Macrobrachium nipponense
Authors: Jiang Sufei , Zhang Wenyi , Xiong Yiwei , Cheng Dan , Wang Jisheng , Jin Shubo , Gong Yongsheng , Wu Yan , Qiao Hui , Fu Hongtuo
Published: August 2022

Background

Macrobrachium nipponenseis an economically and ecologically important freshwater prawn that is widely farmed in China. In contrast to other species of marine shrimp,M. nipponensehas a short sexual maturity period, resulting in not only high stocking densities, but also a reduced survival rate and increased risk of hypoxia. Therefore, there is an urgent need to study the molecular mechanisms underlying fast ovary maturation in this species.

Results

Comparative transcriptome analysis was performed using hepatopancreatic tissue from femaleM. nipponenseacross five ovarian maturation stages to explore differentially expressed genes and pathways involved in ovarian maturation. In total, 118.01 Gb of data were generated from 15 transcriptomes. Approximately 90.46% of clean reads were mapped from theM. nipponensereference genome. A comprehensive comparative analysis between successive ovarian maturation stages generated 230–5814 differentially expressed genes. Gene Ontology (GO) enrichment was highly concentrated in the “biological process” category in all four comparison groups, and mainly focused on energy synthesis and accumulation, energy decomposition and transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that, among 20 significantly enriched KEGG pathways, nine were involved in the synthesis, degradation, and metabolism of carbohydrates, lipids, and other nutrient intermediates, suggesting that the hepatopancreas has an important role in energy supply during ovarian maturation. Furthermore, the “Insect hormone biosynthesis” pathway was found to have a dominant role in the development of the ovary from immaturity to maturity, supporting the hypothesis that ecdysteroid- and juvenile hormone-signaling pathways have an important role in hepatopancreas regulation of ovarian maturation.

Conclusion

Taken together, this study sheds light on the role of the hepatopancreas in the molecular regulation of ovary maturation inM. nipponense. The present study provided new insights for understanding the mechanisms of reproductive regulation in crustaceans.
Differential diagnosis of non-diffuse primary thyroid lymphoma and papillary thyroid carcinoma by ultrasound combined with computed tomography
Authors: Peng Chanjuan , Yi Dan , Zhou Ying , Yao Jincao , Chen Bo , Yang Chen , Xu Dong
Published: August 2022

Background

Primary thyroid lymphoma (PTL) and papillary thyroid carcinoma (PTC) are both thyroid malignancies, but their therapeutic methods and prognosis are different. This study aims to explore their sonographic and computed tomography(CT)features, and to improve the early diagnosis rate.

Methods

The clinical and imaging data of 50 patients with non-diffuse PTL and 100 patients with PTC confirmed by pathology were retrospectively analysed.

Results

Of the 150 patients, from the perspective of clinical data, between non-diffuse PTL and PTC patients existed significant difference in age, maximum diameter of nodule, asymmetric enlargement and Hashimoto’s thyroiditis (P < 0.001), but not in gender ratio, echo texture, cystic change and anteroposterior-to-transverse ratio (P > 0.05). With respect to sonographic feature, non-diffuse PTL patients had a higher proportion than PTC patients in markedly hypoechoic, internal linear echogenic strands, posterior echo enhancement, rich vascularity, lack of calcification and homogeneous enhancement, with statistically significant difference (P < 0.05), while PTC patients had a higher proportion than non-diffuse PTL patients in irregular border, circumscribed margin, capsular invasion and significant enhancement, with statistically significant difference (P < 0.001). With respect to CT feature, non-diffuse PTL patients were significantly different from PTC patients in the non-contrast CT value mean, venous phase CT value mean, enhanced intensity and homogeneity of nodules (P < 0.05). Multivariate logistic regression analysis showed that age (OR = 1.226, 95%CI:1.056 ~ 1.423, P = 0.007), posterior echo enhancement (OR = 51.152, 95%CI: 2.934 ~ 891.738, P = 0.007), lack of calcification (OR = 0.013, 95%CI: 0.000 ~ 0.400, P = 0.013) and homogeneous enhancement (OR = 0.020, 95%CI: 0.001 ~ 0.507, P = 0.018) were independent risk factors.

Conclusions

Sonographic and CT features of the presence of posterior echo enhancement, lack of calcification and homogeneous enhancement were valuable to distinguishing non-diffuse PTL from PTC.
Prevalence and associated factors of corneal arcus in the geriatric population; Tehran geriatric eye study
Authors: Hashemi Hassan , Malekifar Pooneh , Aghamirsalim Mohamadreza , Yekta Abbasali , Mahboubipour Hassan , Khabazkhoob Mehdi
Published: August 2022

Purpose

To determine the age and sex-standardized prevalence of corneal arcus and its associated factors in a geriatric population.

Methods

This population-based cross-sectional study was conducted in 2019 in Tehran; the capital of Iran, using a multi-stage stratified random cluster sampling method. All participants underwent a detailed interview, blood pressure measurement, laboratory blood tests, and a complete ocular examination.

Results

Three thousand three hundred ten of 3791 invitees participated in the study (response rate: 87.31%). The mean age of the participants was 69.35 ± 7.62 years (60–97 years) and 1912 (57.76%) were female. Overall, the age and sex-standardized prevalence (95% CI) of corneal arcus was 44.28% (41.21–47.39). Based on the multiple logistic regression, the odds of corneal arcus were higher in men than in women (OR: 1.51; 95% CI: 1.14–2.00); in the age group ≥ 80 years compared to the age group 60–64 years (OR: 2.44; 95% CI: 1.68–3.53), and in retired people compared to employed individuals (OR: 2.05; 95% CI: 1.31–3.21).

Conclusion

The present study showed a high prevalence of corneal arcus in the geriatric population. Although various studies have reported a significant relationship between corneal arcus with blood lipid and glucose levels as well as blood pressure, these relationships were not found in the present study.
Quality of life and cost-effectiveness analysis of topical tranexamic acid and fibrin glue in femur fracture surgery
Authors: Merchán-Galvis A , Posso M , Canovas E , Jordán M , Aguilera X , Martinez-Zapata MJ
Published: August 2022

Background

We assessed quality of life (QoL) of patients undergoing surgery for proximal femur fracture and performed a cost-effectiveness analysis of haemostatic drugs for reducing postoperative bleeding.

Methods

We analysed data from an open, multicentre, parallel, randomized controlled clinical trial (RCT) that assessed the efficacy and safety of tranexamic acid (TXA group) and fibrin glue (FG group) administered topically prior to surgical closure, compared with usual haemostasis methods (control group).

For this study we conducted a cost-effectiveness analysis of these interventions from the Spanish Health System perspective, using a time horizon of 12 months. The cost was reported in $US purchasing power parity (USPPP). We calculated the incremental cost-effectiveness ratio (ICER) per QALY (quality-adjusted life-year).

Results

We included 134 consecutive patients from February 2013 to March 2015: 42 patients in the TXA group, 46 in the FG group, and 46 in the control group. Before the fracture, EuroQol visual analogue scale (EQ-VAS) health questionnaire score was 68.6. During the 12 months post-surgery, the intragroup EQ-VAS improved, but without reaching pre-fracture values.

There were no differences between groups for EQ-VAS and EuroQol 5 dimensions 5 levels (EQ-5D-5L) health questionnaire score, nor in hospital stay costs or medical complication costs. Nevertheless, the cost of one FG treatment was significantly higher (399.1 $USPPP) than the cost of TXA (12.9 $USPPP) or usual haemostasis (0 $USPPP).

When comparing the cost-effectiveness of the interventions, FG was ruled out by simple dominance since it was more costly (13,314.7 $USPPP) than TXA (13,295.2 $USPPP) and less effective (utilities of 0.0532 vs. 0.0734, respectively). TXA compared to usual haemostasis had an ICER of 15,289.6 $USPPP per QALY).

Conclusions

There were no significant differences between the intervention groups in terms of postoperative changes in QoL. However, topical TXA was more cost-effective than FG or usual haemostasis.

Trial registration

ClinicalTrials.gov: NCT02150720. Date of registration 30/05/2014. Retrospectively registered.
Performance of body mass index and body fat percentage in predicting metabolic syndrome risk factors in diabetic patients of Yazd, Iran
Authors: Shukohifar Marzieh , Mozafari Zohre , Rahmanian Masoud , Mirzaei Masoud
Published: August 2022

Background

Body Fat percentage (BFP) and body mass index (BMI) are used to measure obesity-related metabolic syndrome risk. The present study aimed to determine the values of percent body Fat and body mass index for predicting metabolic syndrome risk factors in diabetic patients of Yazd, Iran.

Methods

A total of 1022 (499 males and 523 females) diabetic patients participated in this study. According to Asian BMI criteria, Overweight was diagnosed if a participant had a BMI ≥25 kg/m2 (both male and female) or BFP ≥25% for male and ≥ 32% for female. Based on calculated BMI and BFP and after adjusting for age, height, weight and smoking habits, the participants were classified into group A (normal weight and Non-Fat), group B (overweight and Non-Fat), group C (normal weight and Fat), and group D (overweight and Fat).

Results

According to the results, the BMI of 23.4% were normal and BMI of 76.6% were overweight, respectively. Moreover, the BFP of 25.7 and 74.3% of the studied population were considered as Non-Fat and Fat, respectively. A strong relationship was found with respect to sex stratification; R2 = 0.79. For men, BMI can be a better predictor of hypertension and hypertriglyceridemia than BFP. For women, BMI was a better predictor of hyperglycemia than BFP. Moreover, BFP can be regarded as a better predictor of hyperglycemia in male group, while it was a good predictor of hypertension and hypertriglyceridemia and hypo HDL than BMI, in female group.

Conclusion

Significant differences were observed between BMI and BFP to predict metabolic syndrome risk factors in diabetic patients across different sexes in our study population. In conclusion, both BMI and BFP should be considered in screening steps.
Non-adherence to medication and associated factors among type 2 diabetes patients at Clinique Medicale Fraternite, Rwanda: a cross-sectional study
Authors: Murwanashyaka Jean de Dieu , Ndagijimana Albert , Biracyaza Emmanuel , Sunday François Xavier , Umugwaneza Maryse
Published: August 2022

Background

Type 2 Diabetes Miletus (T2DM) is a public health burdens that alarmingly increases and leads to morbidity and mortality over the last decades globally. Its management is multifaceted and adherence to diabetic medications plays great roles in life of T2DM patients. But epidemiology on adherence and its associated factors remain unknown in Rwanda. Therefore, this study determined the extent of non-adherence and its predictors among T2DM patients seeking healthcare services at the Clinique Medicale la Fraternite.

Methods

A cross-sectional study among 200 adults’ patients with T2DM receiving care in the Medicale la Fraternite clinic was investigated. Bivariate and multivariate logistic regression models were performed based on odds ratio employed to examine associated predictors of non-adherence. The cut-off value for all statistical significances tests were considered at p < 0.05 with 95% for the confidence intervals.

Results

Overall, more than a half of T2DM patients (53.5%) had poor medication adherence. Being females [OR = 2.1, 95%CI(1.13–3.71), p = 0.002], consuming anti-diabetic drugs for 4–10 years [OR = 2.18, 95%CI(1.09–4.34), p = 0.027], experiencing poor communication with healthcare providers [OR = 2.4; 95%CI (1.36–4.25), p = 0.003] and being perceived as burden of the family [OR = 5.8; 95%CI(1.3–25.7), p < 0.021] had higher odds of non-adherence to anti-diabetic medications. Those with poor HbA1C [OR = 4.26; 95%CI(1.7–10.67), p = 0.002] had 4.26 times higher odds to be non-adherent compared to those with good HbA1C. Respondents with primary [OR = 3.56; 95%CI (1.12–11.28), p = 0.031] and secondary education [OR = 2.96; 95%CI (1.11–7.87), p = 0.03] were more likely to be non-adherent than those with informal education respectively. Those with normal BMI [OR = 5.17; 95%CI(1.63–16.37), p = 0.005] and those with overweight or obese [OR = 3.6; 95%CI (1.04–9.1), p < 0.02] had higher odds of being non-adherent than those with underweight.

Conclusion

Sex, glycaemia, communication with healthcare providers, education and gycosylated hemoglobin were the major predictors of non-adherence. Interventions for tackling this problem through bringing together efforts to stem this epidemic and controlling predictors of non-adherence are urgently recommended.
“If the social circle is engaged, more pregnant women will successfully quit smoking”: a qualitative study of the experiences of midwives in the Netherlands with smoking cessation care
Authors: Willemse Eefje , Walters Bethany Hipple , Springvloet Linda , Bommelé Jeroen , Willemsen Marc C.
Published: August 2022

Background

If smoking is common within a pregnant woman’s social circle, she is more likely to smoke and her chances of succeeding in quitting smoking are reduced. It is therefore important to encourage smoking cessation in a pregnant woman’s social circle. Midwives are ideally positioned to help pregnant women and members of their social circle quit smoking but there is currently little knowledge about if and how midwives approach smoking cessation with pregnant women’s social circles.

Methods

In 2017 and 2018, semi-structured interviews were conducted with 14 birth care providers in the Netherlands. Interviews were inductively coded; data were analyzed thematically.

Results

In the interviews, midwives reported that they don’t commonly provide smoking cessation support to members of pregnant women’s social circles. The respondents noted that they primarily focused on mothers and weren’t always convinced that advising the partners, family, and friends of pregnant women to quit smoking was their responsibility. Data from the interviews revealed that barriers to giving advice to the social circle included a lack of a trusting relationship with the social circle, concerns about raising the topic and giving unwanted advice on cessation to members of the social circle and a lack of opportunity to discuss smoking.

Conclusions

Midwives in the Netherlands were reluctant to actively provide smoking cessation advice to the social circle of pregnant women. To overcome barriers to addressing cessation to the social circle, educational programs or new modules for existing programs could be used to improve skills related to discussing smoking. Clear guidelines and protocols on the role of midwives in providing cessation support to the social circle could help midwives overcome ambivalence that they might have.
Optimising a person-centred approach to stopping medicines in older people with multimorbidity and polypharmacy using the DExTruS framework: a realist review
Authors: Turk Amadea , Wong Geoffrey , Mahtani Kamal R. , Maden Michelle , Hill Ruaraidh , Ranson Ed , Wallace Emma , Krska Janet , Mangin Dee , Byng Richard , Lasserson Daniel , Reeve Joanne
Published: August 2022

Background

Tackling problematic polypharmacy requires tailoring the use of medicines to individual circumstances and may involve the process of deprescribing. Deprescribing can cause anxiety and concern for clinicians and patients. Tailoring medication decisions often entails beyond protocol decision-making, a complex process involving emotional and cognitive work for healthcare professionals and patients. We undertook realist review to highlight and understand the interactions between different factors involved in deprescribing and to develop a final programme theory that identifies and explains components of good practice that support a person-centred approach to deprescribing in older patients with multimorbidity and polypharmacy.

Methods

The realist approach involves identifying underlying causal mechanisms and exploring how, and under what conditions they work. We conducted a search of electronic databases which were supplemented by citation checking and consultation with stakeholders to identify other key documents. The review followed the key steps outlined by Pawson et al. and followed the RAMESES standards for realist syntheses.

Results

We included 119 included documents from which data were extracted to produce context-mechanism-outcome configurations (CMOCs) and a final programme theory. Our programme theory recognises that deprescribing is a complex intervention influenced by a multitude of factors. The components of our final programme theory include the following: a supportive infrastructure that provides clear guidance around professional responsibilities and that enables multidisciplinary working and continuity of care, consistent access to high-quality relevant patient contextual data, the need to support the creation of a shared explanation and understanding of the meaning and purpose of medicines and a trial and learn approach that provides space for monitoring and continuity. These components may support the development of trust which may be key to managing the uncertainty and in turn optimise outcomes. These components are summarised in the novel DExTruS framework.

Conclusion

Our findings recognise the complex interpretive practice and decision-making involved in medication management and identify key components needed to support best practice. Our findings have implications for how we design medication review consultations, professional training and for patient records/data management. Our review also highlights the role that trust plays both as a central element of tailored prescribing and a potential outcome of good practice in this area.
Indirect comparison between powered and manual circular staplers for left-sided colorectal anastomoses: clinical and economic outcomes in China
Authors: Bai Junwei , Zhao Yingnan , Liang Hong , Li Junmeng , Zhang Chao
Published: August 2022

Aims

This study aimed to examine the economic and clinical benefits of a new powered circular stapler for left-sided colorectal construction in China.

Methods

A decision analysis model was constructed for a cohort of adult patients who underwent left-sided colorectal anastomoses, using either the Echelon Circular Powered (ECP) stapler) or the conventional manual circular staplers (MCS). The complications rates and healthcare resource utilization in the ECP cohort were obtained from the single-arm ECP trial (NCT03326895). For the MCS cohort, retrospective data from 20 Chinese hospitals were analyzed. Listing prices were used to estimate the costs of the staplers in China. Propensity score matching (PSM) was employed to adjust for the imbalance between the two cohorts. Anastomotic leak rate, length of stay (LOS), 90-day readmission rate, and direct medical costs were used for the decision analysis model parameters. A budget impact analysis was conducted to compare the total hospitalization expenditure between ECP and manual circular staplers from the hospital’s perspective in China.

Results

Assuming 100 procedures per year, the anastomotic leak rate was 1.79 and 29.76 per 100 procedures in the ECP and MCS cohorts, respectively. LOS was 1,426.91 days in the ECP cohort, compared to 1,702.38 days in the MCS cohort. The 90-day readmission rate was also lower in the ECP cohort than the MCS cohort (19.10 vs. 26.19 per 100 procedures). For the 100 procedures, the annual total hospitalization costs for left-sided colorectal anastomosis were reduced from ¥7,152,251 using manual circular staplers to ¥6,919,306 using ECP. Despite a higher acquisition cost of ECP compared to the manual staplers (¥711,200 vs. ¥441,700), an annual saving of ¥232,945in the total cost resulted from lower rates of complications and shorter LOS. Sensitivity analyses presented consistent savings using ECP, and the ECP cost and cost of the index hospitalization with anastomotic leak were found the most influencing factors.

Conclusions

There were clinical and economic benefits of ECP, compared to manual circular staplers for left-sided colorectal anastomoses. Further direct comparative studies on the use of ECP in practice in Chinese hospital settings are warranted.
Metagenomic analysis of viral diversity and a novel astroviruse of forest rodent
Authors: Yin Hai-chang , Wan De-cai , Chen Hong-yan
Published: August 2022

Background

Rodents are important virus reservoirs and natural hosts for multiple viruses. They are one of the wild animals that are extremely threatening to the spread of human viruses. Therefore, research on rodents carrying viruses and identifying new viruses that rodents carry is of great significance for preventing and controlling viral diseases.

Methods

In this study, fecal samples from six species of forest rodents in Northeast China were sequenced using metagenomics, and an abundance of virome information was acquired. Selection of important zoonotic in individual rodents for further sequence and evolutionary analysis.

Results

Among the top 10 most abundant viral families, RNA virus include Orthomyxoviridae, Picornaviridae, Bunyaviridae and Arenaviridae, DNA virus include Herpesviridae, Insect virus include Nodaviridae and Baculoviridae, Plant virus Tombusviridae and Phage (Myoriviridae). Except for Myoviridae, there was no significant difference in the abundance of virus families in the feces of each rodent species. In addition, a new strain of astrovirus was discovered, with an ORF and genome arrangement comparable to other rodent astroviruses.The newly identified astrovirus had the highest similarity with the rodent astrovirus isolate, CHN/100.

Conclusions

The data obtained in this study provided an overview of the viral community present in these rodent fecal samples, revealing some rodent-associated viruses closely related to known human or animal pathogens. Strengthening our understanding of unclassified viruses harbored by rodents present in the natural environment could provide scientific guidance for preventing and controlling new viral outbreaks that can spread via rodents.
“What you feel under your hands”: exploring professionals’ perspective of somatic dysfunction in osteopathic clinical practice—a qualitative study
Authors: Arcuri Lorenzo , Consorti Giacomo , Tramontano Marco , Petracca Marco , Esteves Jorge Eduardo , Lunghi Christian
Published: August 2022

Background

Despite controversy regarding its validity and clinical usefulness, manual examination findings still have an important role for manipulative therapies. As an example, somatic dysfunction (SD) remains central to osteopathic practice.This study aims to explore the experienced osteopaths' attitudes concerning SD and its role in osteopathic practice. This qualitative research could contribute to building a consistent paradigm for manual intervention in all musculoskeletal manipulations.

Methods

A thematic analysis with grounded theory elements was used. Data were collected through semi-structured interviews carried out between February and April 2021. A purposive sample of twenty professional osteopaths with past experience in osteopathic care was chosen to reflect the phenomenon's variety. The data analysis was done inductively and in tandem with the recruiting to keep track of data saturation.

Results

Eleven osteopaths participated in the study. Three main themes emerged from the data analysis: (1) SD as a safe tissue-touch-based communication tool between operator and person complex adaptive health system; (2) The treatment of SD is shareable between osteopaths, other health professionals, and the patients involved in the therapeutic pathway improving body awareness and health; (3) The development of the SD concept in research and practice to better clarify osteopathic profession identity and definition.

Conclusions

A panel of expert osteopaths consider the concept of SD as a valuable tool integrated into the osteopathic evaluation and treatment process. The shared concept and clinical application of SD is informed by person-centered care concepts and from the fields of neuroscience, cognitive and complexity science. Our study reports a common need among osteopaths to develop an evidence-based framework of SD to allow the best development of the osteopathic profession.
Complications associated with open reduction and internal fixation for adult distal humerus fractures: a multicenter retrospective study
Authors: Han Soo-Hong , Park Jin Sung , Baek Jong Hun , Kim Segi , Ku Ki Hyeok
Published: August 2022

Background

Open reduction and plate fixation are the preferred treatment options for most distal humerus fractures in adults. However, it is often challenging for orthopedic surgeons because of the complex anatomy and the difficulty in achieving stable fixation. This multicenter study aimed to analyze the complication types and rates of patients with distal humerus fractures treated with open reduction and plate fixation, and compare the results with those found in the literature. In addition, we describe the clinical outcomes.

Methods

This retrospective multicenter study was conducted between September 2001 and March 2021 and included data from four hospitals. In total, 349 elbows underwent surgical treatment at these hospitals during the study period. Patients > 17 years of age who were treated by plate fixation were included, and patients who were treated by other fixation methods were excluded. A total of 170 patients were included in the study. The following types of complications were investigated: (1) nerve related; (2) fixation and instrument related; (3) osteosynthesis related; (4) infection; and (5) others.

Results

The following complications were found: (1) 26 (15.3%) cases of postoperative ulnar nerve symptoms; 4 (2.4%) of postoperative radial nerve symptoms; (2) one (0.6%) case of screw joint penetration and screw loosening; and eight (4.7%) cases of hardware removal due to instrument skin irritation; (3) seven (4.1%) cases of nonunion; (4) two (1.2%) and four (2.2%) cases of superficial and deep infection, respectively, and seven (3.9%) cases of wound complication; and (5) 37 (21.8%) cases of heterotrophic ossification, 79 (46.5%) cases of elbow stiffness (did not achieve functional range of motion [ROM]), and 41 (24.1%) cases of osteoarthritis over Broberg and Morrey Grade I.

Paradoxically, the postoperative ulnar nerve symptoms were more frequent in the prophylactic ulnar nerve anterior transposition group. However, this difference was not statistically significant (p = 0.086). The mean ROM was 123.5° flexion to 9.5° extension. The average Disabilities of the Arm, Shoulder and Hand (DASH) score was 14.5 ± 15.6.

Conclusions

Open reduction and plate fixation for distal humeral fractures is a reasonable treatment option with acceptable complication rates and favorable clinical outcomes. Surgeons must be vigilant about ulnar nerve complications.

Level of Evidence Therapeutic Level III.
Identification of RFX5 as prognostic biomarker and associated with immune infiltration in stomach adenocarcinoma
Authors: Guo Lili , Liu Dingsheng
Published: August 2022

Background

Regulatory factor X (RFX) gene family is a series of encodes transcription factors with a highly conserved DNA binding domain. RFXs played a vital role in the development and progression of cancer. However, the significance of RFXs in stomach adenocarcinoma (STAD) has not been fully clarified.

Methods

Online bioinformatics tools such as GSCALite, Kaplan–Meier Plotter, TIMER, LinkedOmics were used to explore the immunomodulatory function and clinical value of RFXs in STAD.

Results

The mRNA level of RFX1, RFX3, RFX4, RFX5, RFX7 and RFX8 was significantly elevated in STAD tissue versus adjacent normal tissue. We also summarize the copy number variation, single nucleotide variants and drug sensitivity of RFXs in STAD. Prognostic analysis indicated that STAD patients with high RFX5 and RFX7 expression had a better overall survival, first progression, and post-progression survival. Moreover, RFX5 expression was significantly associated with the abundance of immune cells, the expression of immune biomarkers and tumor mutational burden score in STAD. Functional enrichment analysis revealed that RFX5 and its related genes were mainly involved in T cell activation, antigen receptor-mediated signaling pathway, cell adhesion molecules, and Th17 cell differentiation. Validation study further verified the expression and prognosis of RFX5 in STAD. Further univariate and multivariate analyses suggested that pathological stage and RFX5 could be a potential independent prognostic factor for STAD.

Conclusions

RFX5 was a candidate prognostic biomarker and associated with immune infiltration in STAD.
Bioanalysis of alpelisib using liquid chromatography–tandem mass spectrometry and application to pharmacokinetic study
Authors: Lee Seop , Kim Min-Soo , Jeong Jong-Woo , Chae Jung-woo , Koo Tae-Sung , Maeng Han-Joo , Chung Suk-Jae , Lee Kyeong-Ryoon , Chae Yoon-Jee
Published: August 2022

Alpelisib is the first alpha-specific phosphatidylinositol-3-kinase (PI3K) inhibitor indicated for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative, PI3K catalytic subunit alpha-mutated, advanced, or metastatic breast cancer. Substantial attempts have been made to extend its clinical use to other types of cancer. Analytical methods proven to accurately quantify alpelisib would improve the reliability of the preclinical and clinical data of alpelisib. Therefore, we developed and validated a quantification method based on liquid chromatography–tandem mass spectrometry for alpelisib in mouse and human plasma samples. Alpelisib and an internal standard (IS; enzalutamide) were separated from endogenous substances using an XTerra MS C18 column with a linear gradient of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Multiple reaction monitoring transitions for alpelisib and the IS were m/z 442.1 > 328.0 and m/z 465.0 > 209.1, respectively. The calibration curve for alpelisib was confirmed to be linear in the range of 1–2000 ng/mL in both mouse and human plasma. The intra- and inter-day accuracy and precision met the acceptance criteria, and no significant matrix effects were observed. Alpelisib was stable under various storage and handling conditions, and the carryover effect was overcome using the injection loop flushing method. We successfully used this assay to study the in vitro metabolic profiles and in vivo pharmacokinetics of alpelisib in mice. Here, to the best of our knowledge, we report for the first time a valid quantitative method for alpelisib in mouse and human plasma, which could aid in providing valuable pharmacokinetic information on alpelisib to increase its clinical availability.
3D render volume CT reconstruction of the bones and arteries of the hind digit of the dromedary camel (Camelus dromedarius)
Authors: El-Gendy Samir A. A. , Kamal Basma M. , Alsafy Mohamed A. M.
Published: August 2022

Background

The 3D computed tomography produces detailed images of the digit bones in addition to the angiograph render volume 3D of the CT shows the relation between the arteries, bones, and tissues of the digit. Therefore, the present study used those imaging techniques to provide a complete description of the digit bones and arteries’ origin, distribution, and course and their relations with surrounding structures in the Dromedary Camel. Which would serve as a guide for surgeons and students in distinguishing normal digit structures. The study used eight hind limbs of four adult camels of both sexes (two males and two females), aged 9–15 years (Mean ± SD, 11.80 ± 2.59 years). The samples were injected with latex with lead oxide were undergone 3D render volume CT (128-slice multi-detector CT scanning protocol) and angiography x-rays.

Results

The blood vessels and correlated structures such as bones, tendons, and ligaments were examined using 3D CT in all directions, which was easier to view than angiography and dissected specimens. The arterial supply to the camel’s hind foot was the A. digitalis plantaris communis III. The angiography render volume 3D of CT explained the blood supply of the bones and joints of digital regions and showed a good visualization of the many digit arteries. The metatarsals, the phalanges, and the sesamoid bones were visualized. A. plantaris medialis superficialis, A. digitalis plantaris communis III, A. digitalis plantaris communis II and IV, A. interdigitalis, rami articularis medialis and lateralis to the fetlock joint, ramus medialis and ramus lateralis of the A. digitalis plantaris communis III, A. digitalis plantaris propriae III et IV abaxialis, A. digitalis plantaris propriae III et IV axialis, Ramus phalangis axialis and abaxialis of the first phalanx, Ramus phalangis axialis and abaxialis of the second and third phalanges, and A. metatarsae plantaris III were visualized. The study discovered new blood vessel sources in dromedary camels, such as the ramus articularis to the fetlock and the ramus plantaris phalangis abaxialis proximalis and distalis of the first phalanx.

Conclusions

The digital circulation angiography investigates the circulatory pattern of the camel hind digit, which can assist clinicians in diagnosing digit region affections. 3D CT explained improved visualization of bones and arteries, including many small branches in relation to surrounding structures, in some views better than others.
General anesthesia for treating scoliosis with congenital myasthenia syndrome: a case report
Authors: Yamashita Atsushi , Muramatsu Yuka , Matsuda Hiromi , Okamoto Hirotsugu
Published: August 2022

Background

Congenital myasthenia syndrome is a heterogeneous disease with impaired neuromuscular transmission.

Case presentation

This report describes a 13-year-old child with congenital myasthenia syndrome who underwent surgery for scoliosis under general anesthesia. We used a small dose of rocuronium, neuromuscular transmission monitoring, and non-invasive positive pressure ventilation for postoperative respiratory management. There were no respiratory complications during the perioperative period.

Conclusion

As there are only a few reports on the anesthetic management of patients with congenital myasthenia syndrome, we applied the principles of managing autoimmune myasthenia gravis. The postoperative management described herein can prevent respiratory complications in patients with congenital myasthenia syndrome.
How to locate the dural defect in a spinal extradural meningeal cyst: a literature review
Authors: Jian Qiang , Liu Zhenlei , Duan Wanru , Jian Fengzeng , Chen Zan
Published: August 2022

Spinal extradural meningeal cysts (SEMCs) are rare lesions of the spinal canal. Although closure of the dural defect can achieve satisfactory therapeutic effects, locating the fistula is difficult. This review summarizes the methods for locating the fistula of SEMCs and the distribution and features of fistula sites.

This was a non-systematic literature review of studies on SEMCs. We searched PubMed for English-language articles to summarize the methods of locating the defect. The search words were “epidural arachnoid cyst,” “dural cyst,” “epidural cyst,” and “epidural meningeal cyst.” For the defect location component of the study, case reports, studies with a sample size less than four, controversial ventral dural dissection(s), and undocumented fistula location reports were excluded.

Our review showed that radiography and computed tomography (CT) may show changes in the bony structure of the spine, with the largest segment of change indicating the fistula site. Occasionally, magnetic resonance imaging (MRI) can show a cerebrospinal fluid (CSF) flow void at the fistula site. The middle segment of the cyst on sagittal MRI, the largest cyst area, and cyst laterality in the axial view indicate the fistula location. Myelography can show the fistula location in the area of the enhanced cyst and subarachnoid stenosis. Digital subtraction or delayed CT can be used to observe the location of the initial cyst filling. Cine MRI and time-spatial labeling inversion pulse techniques can be used to observe CSF flow. Steady-state image construction interference sequence MRI has a high spatial resolution. Neuroendoscopy, MRI myelography, and ultrasound fistula detection can be performed intraoperatively. Moreover, the fistula was located most often in the T12–L1 segment.

Identifying the fistula location is difficult and requires a combination of multiple examinations and experience for comprehensive judgment.
Image quality and subject experience of quiet T1-weighted 7-T brain imaging using a silent gradient coil
Authors: Jacobs Sarah M. , Versteeg Edwin , van der Kolk Anja G. , Visser Leonie N. C. , Oliveira Ícaro A. F. , van Maren Emiel , Klomp Dennis W. J. , Siero Jeroen C. W.
Published: August 2022

Objectives

Acoustic noise in magnetic resonance imaging (MRI) negatively impacts patients. We assessed a silent gradient coil switched at 20 kHz combined with a T1-weighted magnetisation prepared rapid gradient-echo (MPRAGE) sequence at 7 T.

Methods

Five healthy subjects (21–29 years; three females) without previous 7-T MRI experience underwent both a quiet MPRAGE (Q-MPRAGE) and conventional MPRAGE (C-MPRAGE) sequence twice. Image quality was assessed quantitatively, and qualitatively by two neuroradiologists. Sound level was measured objectively and rated subjectively on a 0 to 10 scale by all subjects immediately following each sequence and after the whole examination (delayed). All subjects also reported comfort level, overall experience and willingness to undergo the sequence again.

Results

Compared to C-MPRAGE, Q-MPRAGE showed higher signal-to-noise ratio (10%; p = 0.012) and lower contrast-to-noise ratio (20%; p < 0.001) as well as acceptable to good image quality. Q-MPRAGE produced 27 dB lower sound level (76 versus 103 dB). Subjects reported lower sound level for Q-MPRAGE both immediate (4.4 ± 1.4 versus 6.4 ± 1.3; p = 0.007) and delayed (4.6 ± 1.4 versus 6.3 ± 1.3; p = 0.005), while they rated comfort level (7.4 ± 1.0 versus 6.1 ± 1.7; p = 0.016) and overall experience (7.6 ± 1.0 versus 6.0 ± 0.9; p = 0.005) higher. Willingness to undergo the sequence again was also higher, however not significantly (8.1 ± 1.0 versus 7.2 ± 1.3; p = 0.066).

Conclusion

Q-MPRAGE using a silent gradient coil reduced sound level by 27 dB compared to C-MPRAGE at 7 T while featuring acceptable-to-good image quality and a quieter and more pleasant subject experience.
Impact of using Sarcophaga (Liopygia) argyrostoma (Robineau-Desvoidy, 1830) as a toxicological sample in detecting clonazepam for forensic investigation
Authors: Afifi Fatma Mohamed , Abdelfattah Eman Alaaeldin , El-Bassiony Ghada Mohamed
Published: August 2022

Background

Sarcophagidae along with Calliphoridae (superfamily Oestroidea) were known as important colonizers of cadavers and could be used to estimate the postmortem interval (PMI), through tracking the flies colonizing pattern and/or monitoring their growth rates on cadavers. Many previous researches discussed the impact of toxins in decomposing corpses, on the developmental stages of insects, which would affect the accuracy of PMI estimation. Clonazepam belongs to the benzodiazepines, and it is one of the most routinely used drugs to control humans’ seizures. The current study aimed to investigate the effect of clonazepam on the developmental stages of Sarcophaga argyrostoma, one of the most widespread Sarcophagidae in Giza Governorate. Also, we investigate the ability of these developmental stages to detect the drug.

Results

The current study used different concentrations of clonazepam (25, 50, and 100 mg/ml) as an in vitro application of the flesh fly S. argyrostoma. The drug has affected significantly the morphological measurements (weight, length, and width) of the different developmental stages, especially in the highest concentration (100 mg/ml). Quantitative and qualitative analyses were applied, by using high-performance liquid chromatography-mass spectrometry (HPLC–MS) and protein carbonyls amount respectively, to detect clonazepam in the second, early third, and late third larval instars and prepupa of S. argyrostoma. The results showed that the relationship between the concentration of the drug and its detection in the same developing instar is interdependent, using HPLC–MS. However, the drug faded from instar to the following one and transformed to its metabolite form. Measuring the protein carbonyls amount (OD/mg protein/min) revealed an elevation in the macromolecules damage, compared to the control groups, in almost all treated groups.

Conclusions

The current data suggested that clonazepam has oxidative damage in S. argyrostoma. While HPLC–MS was efficient in measuring the concentration of the drug in the insect, protein carbonyls analysis was a time- and cost-saving method and could be used to detect the drug in insects qualitatively.

Graphical abstract