bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of groundnut shell powder as a potential reinforcement for biocomposites
Authors: Usman Mohammed Awwalu , Momohjimoh Ibrahim , Usman Abdulhafiz Onimisi
Published: August 2021

Natural fibers are becoming the right candidate material as a substitute for glass fibers in the reinforcement of plastic polymers for various applications. The ease of their processing with minimal energy consumption and the quest to produce biodegradable plastics with lightweight has given natural fibers comparative advantages over synthetic fibers. In this study, groundnut shell powder (GSP) in different forms (untreated, sodium hydroxide treated and ash) were characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR), X-ray fluorescence (XRF), Nuclear magnetic resonance (NMR), Differential scanning calorimetry (DSC) and Scanning electron microscopy (SEM) to evaluate their possible utilization as reinforcement in polymers. GSP was treated with sodium hydroxide for 5 hrs and dried in vacuum for 24 hrs to obtain treated GSP while ash GSP was formed by heating GSP in the furnace at 600 °C for about 3 hrs. The results reveal that sodium hydroxide treatment was very effective in the breaking down of the hydrogen bond with a consequent reduction in the hydrophilicity of the GSP. This would promote GSP bonding with the hydrophobic polymer matrix in the development of natural fiber reinforced plastic polymer composite materials. Ash GSP was found to have the highest crystallinity among the three forms of GSP based on XRD results. Therefore, the result achieved in this work confirmed that treated and ash GSP fibers are good reinforcement material in the production of polymer composites, with the actual choice depending on end-use property requirements of the composite.
A modified ileal conduit technique in patients undergoing radical cystectomy: Single-centre experience
Authors: Chiancone Francesco , Persico Francesco , Fabiano Marco , Fedelini Maurizio , Meccariello Clemente , Fedelini Paolo
Published: August 2021

Objective:

We aimed to evaluate perioperative outcomes and complications of a modified technique of ileal conduit diversion.

Methods:

Forty-seven cases of radical cystectomy with modified ileal conduit diversion were performed at our institution from January 2015 to January 2020. After radical cystectomy, a segment of ileum was used to pack the conduit and was placed below the digestive anastomosis. Then, the mesentery window of the ileo-ileal anastomosis was sutured. The ureters were anastomosed on their native side on single loop ureteral stents. All procedures were performed by a single surgical team. Intra- and postoperative complications were classified and reported according to the Satava and Clavien–Dindo grading systems.

Results:

The mean age of population was 66.40±10.14 years, and 76.6% were male. Concomitant diabetes was found in 31.9% of patients. About three quarters of patients had T2G3 bladder cancer. Mean blood loss was 449.36±246.50 ml, and hospitalization was 10.32±5 days. With a mean follow-up of 17.36±12.63 months, the recurrence rate was 17%, and 14.9% of patients died of bladder cancer. Out of the 47 patients, three (4.3%) experienced intraoperative complications, while 15 (31.9%) had postoperative complications. Of these, only three patients experienced Clavien–Dindo complications ⩾grade 3. Multivariate logistic regression model showed that diabetes ( p=0.023) and higher blood loss ( p=0.010) were significantly associated with an increased risk of postoperative complications. We reported one case of ureterointestinal anastomosis stenosis on the left side and none on the right side. Despite our results being promising, larger randomized trials with longer follow-up are needed to explore further the feasibility of this technique on a larger scale.

Conclusion:

We describe a safe and simple surgical technique with a similar postoperative complications rate and a lower incidence of ureteroileal anastomosis stenosis compared to the standard technique.

Level of evidence

4.
Disseminated intravascular coagulation and its immune mechanisms
Authors: Popescu Narcis I. , Lupu Cristina , Lupu Florea
Published: August 2021

Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and noninfectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of the contact pathway in response to pathogen-associated or host-derived, damage-associated molecular patterns. The process is further amplified through inflammatory and immunothrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients is associated with worsening morbidities and increased mortality, regardless of the underlying pathology; therefore, timely recognition of DIC is critical for reducing the pathologic burden. Due to the diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia, and fibrinogen conversion. Because current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of nonovert DIC and/or pre-DIC states. Therapeutic strategies for patients with DIC involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in patients with DIC remains high, and new strategies, tailored to the underlying pathologic mechanisms, are needed.
Clinicopathological features and survival in EBV-positive diffuse large B-cell lymphoma not otherwise specified
Authors: Bourbon Estelle , Maucort-Boulch Delphine , Fontaine Juliette , Mauduit Claire , Sesques Pierre , Safar Violaine , Ferrant Emmanuelle , Golfier Camille , Ghergus Dana , Karlin Lionel , Lazareth Anne , Bouafia Fadhela , Pica Gian Matteo , Orsini-Piocelle Frédérique , Rocher Clément , Gros François-Xavier , Parrens Marie , Dony Arthur , Rossi Cédric , Ghesquières Hervé , Bachy Emmanuel , Traverse-Glehen Alexandra , Sarkozy Clémentine
Published: August 2021

In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (>50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio [HR], 14.01; 95% confidence interval [CI], 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV− DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients >50 years (5-year OS, 53% [95% CI, 38.2-74] vs 60.8% [95% CI, 55.4-69.3], P = .038), but not in younger patients.
Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1
Authors: Obiorah Ifeyinwa Emmanuela , Patel Bhavisha A. , Groarke Emma M. , Wang Weixin , Trick Megan , Ombrello Amanda K. , Ferrada Marcela A. , Wu Zhijie , Gutierrez-Rodrigues Fernanda , Lotter Jennifer , Wilson Lorena , Hoffmann Patrycja , Cardona Daniela Ospina , Patel Nisha , Dulau-Florea Alina , Kastner Daniel L. , Grayson Peter C. , Beck David B. , Young Neal S. , Calvo Katherine R.
Published: August 2021

Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.
Co-creating opportunities to incorporate cessation for electronic nicotine delivery systems in family medicine – a qualitative program evaluation
Authors: Kovach Kevin A. , Peterson Reshana , Bharati Rajani , Istas Kathryn , Monroe Michael
Published: August 2021

Background

The number of Americans who use tobacco has decreased in the twenty-first century, but electronic nicotine delivery systems (ENDS) have increased the complexity of treating tobacco dependence. The experiences of 18 family medicine practices were explored and opportunities to improve ENDS cessation were co-created in this study.

Methods

Eighteen family medicine practices were enrolled into an implementation project to incorporate ENDS cessation into their practice. The participants’ experiences were explored throughout the project using an iterative qualitative approach. The research team provided technical assistance. Semi-structured group interviews and focus groups were held with participants at the beginning, middle, and end of the project to explore participants’ experiences. The collective knowledge and experiences of participants, expert consultants and the research team were fused together to co-create opportunities to improve ENDS cessation.

Results

Nine opportunities to improve ENDS cessation were identified in three larger categories. The first category was leading change. This included: creating a vision for change to establish buy-in from key stakeholders and educate health care professionals to improve their confidence to address ENDS. The second category was creating processes. This included: establishing criteria for screening and quality improvement for ENDS cessation; being specific when asking about ENDS; creating electronic health record systems to support incorporating ENDS cessation; using chart audits if electronic health records cannot support incorporating ENDS into tobacco cessation; and assigning roles and responsibilities to members of the clinical care team. The third category was assisting patients who use ENDS. This included: educating patients and their parents/caregivers about ENDS and their potential harms, avoiding dual use, and developing a plan to quit.

Conclusions

This study highlights challenges and opportunities for incorporating ENDS cessation into family medicine. The opportunities outlined here provide a practical approach which is rooted in the experiences of family physicians and their clinical care teams working to improve how they address ENDS and based on peer reviewed literature and expert input. Improving how ENDS are addressed in family medicine will require more than clinical expertise. It will also require leadership skills and the ability to create process improvements.

Trial registration

Not applicable
Translation and validation of the German version of the Young Spine Questionnaire
Authors: Nyirö Luana , Potthoff Tobias , Siegenthaler Mette Hobaek , Riner Fabienne , Schweinhardt Petra , Wirth Brigitte
Published: August 2021

Background

Back pain in childhood and adolescence increases the risk for back pain in adulthood, but validated assessment tools are scarce. The aim of this study was to validate the Young Spine Questionnaire (YSQ) in a German version (G-YSQ) in children and adolescents.

Methods

Children and adolescents between 10 and 16 years (N = 240, 166 females, mean age = 13.05 ± 1.70 years), recruited in chiropractic practices and schools, completed the G-YSQ (translated according to scientific guidelines) and the KIDSCREEN-10 (assessing health-related quality of life) at three time points. Test-retest reliability was determined calculating intraclass correlation coefficients [ICC(3,1)] using start and two week-data. Construct validity was investigated testing a priori hypotheses. To assess responsiveness, the patients additionally filled in the Patient Global Impression of Change (PGIC) after three months and the area under the curve (AUC) of receiver operating curves was calculated.

Results

The ICC(3,1) was 0.88 for pain intensity and pain frequency, indicating good reliability, 0.68 for week prevalence and 0.60 for point prevalence, indicating moderate reliability. Pain intensity, frequency and prevalence differed between patients and controls (p < 0.001) and, except point prevalence, between older (> 12 years) and younger control participants (p < 0.01). Health-related quality of life of participants with severe pain (in one or several spinal regions) was lower (KIDSCREEN-10, total score: F(4,230) = 7.26, p < 0.001; KIDSCREEN-10, self-rated general health: H(4) = 51.94, p < 0.001) than that of participants without pain or with moderate pain in one spinal region. Thus, altogether these findings indicate construct validity of the G-YSQ. The AUC was 0.69 (95 % CI = 0.57–0.82) and 0.67 (95 % CI = 0.54–0.80) for week and point prevalence, respectively, indicating insufficient responsiveness of the G-YSQ.

Conclusions

Apart from the question on point prevalence, construct validity and sufficient test-retest reliability was shown for the G-YSQ. However, its responsiveness needs to be improved, possibly by asking for pain frequency during the last week instead of (dichotomous) week prevalence.

Trial registration

ClinicalTrials.gov, NCT02955342, registered 07/09/2016, https://clinicaltrials.gov/ct2/results?cond=&term=NCT02955342&cntry=CH&state=&city=Zurich&dist=.
Problem-solving training as an active ingredient of treatment for youth depression: a scoping review and exploratory meta-analysis
Authors: Krause Karolin R. , Courtney Darren B. , Chan Benjamin W. C. , Bonato Sarah , Aitken Madison , Relihan Jacqueline , Prebeg Matthew , Darnay Karleigh , Hawke Lisa D. , Watson Priya , Szatmari Peter
Published: August 2021

Background

Problem-solving training is a common ingredient of evidence-based therapies for youth depression and has shown effectiveness as a versatile stand-alone intervention in adults. This scoping review provided a first overview of the evidence supporting problem solving as a mechanism for treating depression in youth aged 14 to 24 years.

Methods

Five bibliographic databases (APA PsycINFO, CINAHL, Embase, MEDLINE, Web of Science) and the grey literature were systematically searched for controlled trials of stand-alone problem-solving therapy; secondary analyses of trial data exploring problem-solving-related concepts as predictors, moderators, or mediators of treatment response within broader therapies; and clinical practice guidelines for youth depression. Following the scoping review, an exploratory meta-analysis examined the overall effectiveness of stand-alone problem-solving therapy.

Results

Inclusion criteria were met by four randomized trials of problem-solving therapy (524 participants); four secondary analyses of problem-solving-related concepts as predictors, moderators, or mediators; and 23 practice guidelines. The only clinical trial rated as having a low risk of bias found problem-solving training helped youth solve personal problems but was not significantly more effective than the control at reducing emotional symptoms. An exploratory meta-analysis showed a small and non-significant effect on self-reported depression or emotional symptoms (Hedges’ g = − 0.34; 95% CI: − 0.92 to 0.23) with high heterogeneity. Removing one study at high risk of bias led to a decrease in effect size and heterogeneity (g = − 0.08; 95% CI: − 0.26 to 0.10). A GRADE appraisal suggested a low overall quality of the evidence. Tentative evidence from secondary analyses suggested problem-solving training might enhance outcomes in cognitive-behavioural therapy and family therapy, but dedicated dismantling studies are needed to corroborate these findings. Clinical practice guidelines did not recommend problem-solving training as a stand-alone treatment for youth depression, but five mentioned it as a treatment ingredient.

Conclusions

On its own, problem-solving training may be beneficial for helping youth solve personal challenges, but it may not measurably reduce depressive symptoms. Youth experiencing elevated depressive symptoms may require more comprehensive psychotherapeutic support alongside problem-solving training. High-quality studies are needed to examine the effectiveness of problem-solving training as a stand-alone approach and as a treatment ingredient.
Giant cell tumors of the mobile spine with invasion of adjacent vertebrae: an unusual imaging finding
Authors: Jiang Gang , Sun Ling-Ling , Ye Yong-Jun , Yang Zhi-Tao , Ji Qing-lian , Pang Jing , Gao Chuan-Ping
Published: August 2021

Background

Giant cell tumors of the mobile spine invasion of the adjacent vertebrae are an ignored imaging finding.

Methods

Nine patients with giant cell tumors of the mobile spine with invasion of the adjacent vertebrae confirmed by pathology were enrolled. Eight patients had pure giant cell tumors (GCTs), while one patient also had an aneurysmal bone cyst. All patients underwent conventional computed tomography, three-dimensional reconstruction, and conventional magnetic resonance imaging, while seven patients also underwent post-contrast magnetic resonance imaging.

Results

All patients showed GCTs of the mobile spine that arose from the vertebral body and extended to the vertebral arch. The tumors showed soft-tissue attenuation with no evidence of a mineralized matrix. Pathological fracture was seen in five patients. The margin of the original tumor showed partial sclerosis in four patients and involved an adjacent vertebral body with a sclerotic rim in two patients. The tumors showed a homogeneous and similar signal intensity to the normal spinal cord on T1WI (T1-weighted image) in five patients. The cystic area of the tumors was hyperintense on T2WI in the remaining four patients, while one patient showed hemorrhage that was hyperintense on T1WI. The solid components of the GCTs show marked enhancement in all cases, while the cystic area of the tumors was observed without enhancement on contrast-enhanced images in four patients. Bone destruction of the adjacent vertebral body showed a homogeneous signal on T1WI and T2WI and marked enhancement on contrast-enhanced images.

Conclusions

Giant cell tumors of the mobile spine with invasion into adjacent vertebrae are an unusual imaging finding. Radiologists should be familiar with this imaging characteristic.
Smoking induces sex-specific changes in the small airway proteome
Authors: Kokelj Spela , Östling Jörgen , Georgi Benjamin , Fromell Karin , Ekdahl Kristina Nilsson , Olsson Henric K. , Olin Anna-Carin
Published: August 2021

Introduction

Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking.

Methods

Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed.

Results

Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers.

Conclusions

The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.
Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells
Authors: Wang Hongxia , Wang Liyan , Li Yanning , Li Guangqi , Zhang Xiaochun , Jiang Dan , Zhang Yanting , Liu Liyuan , Chu Yuankui , Xu Guangxian
Published: August 2021

Background

Taking advantage of nanobodies (Nbs) in immunotherapy, we investigated the cytotoxicity of Nb-based chimeric antigen receptor T cells (Nb CAR-T) against lymphoma cells.

Methods

CD19 Nb CAR-T, CD20 Nb CAR-T, and Bispecific Nb CAR-T cells were generated by panning anti-human CD19- and CD20-specific nanobody sequences from a natural Nb-expressing phage display library, integrating Nb genes with a lentiviral cassette that included other CAR elements, and finally transducing T cells that were expanded under an optimization system with the above generated CAR lentivirus. Prepared Nb CAR-T cells were cocultured with tumour cell lines or primary tumour cells for 24 h or 5 days to evaluate their biological function.

Results

The nanobodies that we selected from the natural Nb-expressing phage display library had a high affinity and specificity for CD19 and CD20. CD19 Nb CAR-T, CD20 Nb CAR-T and Bispecific Nb CAR-T cells were successfully constructed, and these Nb CAR-T cells could strongly recognize Burkitt lymphoma cell lines (Raji and Daudi), thereby leading to activation, enhanced proliferation, and specific killing of target cells. Furthermore, similar results were obtained when using patient samples as target cells, with a cytotoxicity of approximately 60%.

Conclusions

Nanobody-based CAR-T cells can kill both tumour cell lines and patient-derived tumour cells in vitro, and Nb-based CAR-T cells may be a promising therapeutic strategy in future immunotherapy.
miR-499a inhibits the proliferation and apoptosis of prostate cancer via targeting UBE2V2
Authors: Chen Yougan , Sun Fanghao , Zhang Liansheng , Zhou Jian , Hou Jianquan
Published: August 2021

Background

Prostate cancer is one of the malignant tumors of the urinary system and ranks second among the fatal cancers in men. And with age, the incidence of prostate cancer will increase linearly.

Methods

In this study, we measured the expression of Ubiquitin Conjugating Enzyme E2 V2 (UBE2V2) in prostate cancer tissues and cell lines by WB and explored the effect of UBE2V2 on the proliferation characteristics of prostate cancer by MTT and colony formation test.

Results

In our research, we found that the UBE2V2 protein level in prostate cancer cell lines was significantly higher than the UBE2V2 protein level in normal prostate cells, and the mRNA expression level did not change significantly compared with normal prostate tissue cells. At the same time, we found that miR-499a combined with UBE2V2 inhibited the expression of UBE2V2 in prostate cancer cells.

Conclusions

In conclusion, our results indicate that miR-499a inhibits the proliferation of human prostate cancer cells by targeting UBE2V2, which will provide a potential target for the treatment of prostate cancer.
Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia
Authors: Tang Dongdong , Lv Mingrong , Gao Yang , Cheng Huiru , Li Kuokuo , Xu Chuan , Geng Hao , Li Guanjian , Shen Qunshan , Wang Chao , He Xiaojin , Cao Yunxia
Published: August 2021

Background

Non-obstructive azoospermia (NOA) is the most severe form of male infertility; more than half of the NOA patients are idiopathic. Although many NOA risk genes have been detected, the genetic factors for NOA in majority of the patients are unknown. In addition, it is difficult to retrieve sperm from these patients despite using the microsurgical testicular sperm extraction (microTESE) method. Therefore, we conducted this genetic study to identify the potential genetic factors responsible for NOA and investigate the sperm retrieval rate of microTESE for genetically deficient NOA patients.

Methods

Semen analyses, sex hormone testing, and testicular biopsy were performed to categorize the patients with NOA. The chromosome karyotypes and Y chromosome microdeletion analyses were used to exclude general genetic factors. Whole exome sequencing and Sanger sequencing were performed to identify potential genetic variants in 51 patients with NOA. Hematoxylin and eosin staining (H&E) and anti-phosphorylated H2AX were used to assess the histopathology of spermatogenesis. Quantitative real time-polymerase chain reaction, western blotting, and immunofluorescence were performed to verify the effects of gene variation on expression.

Results

We performed whole exome sequencing in 51 NOA patients and identified homozygous helicase for meiosis 1(HFM1) variants (NM_001017975: c.3490C > T: p.Q1164X; c.3470G > A: p.C1157Y) in two patients (3.9%, 2/51). Histopathology of the testis showed that spermatogenesis was completely blocked at metaphase in these two patients carrying the HFM1 homozygous variants. In comparison with unaffected controls, we found a significant reduction in the levels of HFM1 mRNA and protein expression in the testicular tissues from these two patients. The patients were also subjected to microTESE treatment, but the sperms could not be retrieved.

Conclusions

This study identified novel homozygous variants of HFM1 that are responsible for spermatogenic failure and NOA, and microTESE did not aid in retrieving sperms from these patients.
Differences and similarities in clinical and functional responses among patients receiving tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate: a post hoc analysis of data from ORAL Strategy
Authors: Takeuchi Tsutomu , Fleischmann Roy , Iikuni Noriko , Shi Harry , Soma Koshika , Paulissen Jerome , Hirose Tomohiro , Smolen Josef S.
Published: August 2021

Background

This post hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots.

Methods

In the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in the Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in the Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤ 2.8) status at months 6 and 12.

Results

Data for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not.

Conclusions

These results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre-treatment CRP levels may be associated with better response to tofacitinib + MTX.

Trial registration

ClinicalTrials.gov, NCT02187055. Registered on 08 July 2014.
Neuroprotection in early stages of Alzheimer’s disease is promoted by transthyretin angiogenic properties
Authors: Gião Tiago , Saavedra Joana , Vieira José Ricardo , Pinto Marta Teixeira , Arsequell Gemma , Cardoso Isabel
Published: August 2021

Background

While still controversial, it has been demonstrated that vascular defects can precede the onset of other AD hallmarks features, making it an important therapeutic target. Given that the protein transthyretin (TTR) has been established as neuroprotective in AD, here we investigated the influence of TTR in the vasculature.

Methods

We evaluated the thickness of the basement membrane and the length of brain microvessels, by immunohistochemistry, in AβPPswe/PS1A246E (AD) transgenic mice and non-transgenic mice (NT) bearing one (TTR+/−) or two (TTR+/+) copies of the TTR gene. The angiogenic potential of TTR was evaluated in vitro using the tube formation assay, and in vivo using the chick chorioallantoic membrane (CAM) assay.

Results

AD transgenic mice with TTR genetic reduction, AD/TTR+/−, exhibited a thicker BM in brain microvessels and decreased vessel length than animals with normal TTR levels, AD/TTR+/+. Further in vivo investigation, using the CAM assay, revealed that TTR is a pro-angiogenic molecule, and the neovessels formed are functional. Also, TTR increased the expression of key angiogenic molecules such as proteins interleukins 6 and 8, angiopoietin 2, and vascular endothelial growth factor, by endothelial cells, in vitro, under tube formation conditions. We showed that while TTR reduction also leads to a thicker BM in NT mice, this effect is more pronounced in AD mice than in NT animals, strengthening the idea that TTR is a neuroprotective protein. We also studied the effect of TTR tetrameric stabilization on BM thickness, showing that AD mice treated with the TTR tetrameric stabilizer iododiflunisal (IDIF) displayed a significant reduction of BM thickness and increased vessel length, when compared to non-treated littermates.

Conclusion

Our in vivo results demonstrate the involvement of TTR in angiogenesis, particularly as a modulator of vascular alterations occurring in AD. Since TTR is decreased early in AD, its tetrameric stabilization can represent a therapeutic avenue for the early treatment of AD through the maintenance of the vascular structure.
Stressful life events among incarcerated women and men: Association with depression, loneliness, hopelessness, and suicidality
Authors: Moore Kelly E. , Siebert Shania , Brown Garrett , Felton Julia , Johnson Jennifer E.
Published: August 2021

Background

Justice-involved populations report a higher than average number of pre-incarceration stressful life events. However, few studies have described stressful life events which occur during incarceration, explored gender differences in these events, or evaluated the effect of these events on well-being.

Method

This study draws from a sample of male and female adults incarcerated in 6 prison facilities across two states (n = 160) to identify the number and type of stressful life events they experienced during incarceration, gender differences in stressful events, and the relationship between stressful life events and markers of well-being (i.e., depression, hopelessness, loneliness, suicidality). We also examined whether perceived social support would buffer the relationship between stressful events and well-being outcomes.

Results

Participants on average reported experiencing 4 stressful life events during their current incarceration, the most common being relocation to another cell and being made fun of/insulted by someone in the prison. There were few gender differences in types of events experienced. Regression analyses showed that stressful life events were associated with more loneliness, as well as suicidality, but only when participants had low perceived social support.

Conclusions

Stressful life events, and drawing on social support networks to cope with stress, should be addressed in the context of correctional treatments to reduce suicide risk during incarceration.
Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality
Authors: Frigyesi Attila , Lengquist Maria , Spångfors Martin , Annborn Martin , Cronberg Tobias , Nielsen Niklas , Levin Helena , Friberg Hans
Published: August 2021

Background

Our aim was to investigate the prognostic potential of circulating dipeptidyl peptidase 3 (cDPP3) to predict mortality and development of organ dysfunction in a mixed intensive care unit (ICU) population, and for this reason, we analysed prospectively collected admission blood samples from adult ICU patients at four Swedish hospitals. Blood samples were stored in a biobank for later batch analysis. The association of cDPP3 levels with 30-day mortality and Sequential Organ Failure Assessment (SOFA) scores on day two was investigated before and after adjustment for the simplified acute physiology score III (SAPS-3), using multivariable (ordinal) logistic regression. The predictive power of cDPP3 was assessed using the area under the receiver operating characteristic curve (AUROC).

Results

Of 1978 included consecutive patients in 1 year (2016), 632 fulfilled the sepsis 3-criteria, 190 were admitted after cardiac arrest, and 157 because of trauma. Admission cDPP3 was independently (of SAPS-3) associated with 30-day mortality with odds ratios of 1.45 (95% confidence interval (CI) 1.28–1.64) in the entire ICU population, 1.30 (95% CI 1.08–1.57) in the sepsis subgroup and 2.28 (95% CI 1.50–3.62) in cardiac arrest. For trauma, there was no clear association. Circulating DPP3 alone was a moderate predictor of 30-day mortality with AUROCs of 0.68, 0.62, and 0.72 in the entire group, the sepsis subgroup, and the cardiac arrest subgroup, respectively. By adding cDPP3 to SAPS-3, AUROC improved for the entire group, the sepsis subgroup, and the cardiac arrest subgroup (p = 0.023).

Conclusion

Circulating DPP3 on admission is a SAPS-3 independent prognostic factor of day-two organ dysfunction and 30-day mortality in a mixed ICU population and needs further evaluation.
Bacterial arthritis of native joints can be successfully managed with needle arthroscopy
Authors: Stornebrink Tobias , Janssen Stein J. , Kievit Arthur J. , Mercer Nathaniel P. , Kennedy John. G. , Stufkens Sjoerd A. S. , Kerkhoffs Gino M. M. J.
Published: August 2021

Purpose

To assess the feasibility of needle arthroscopy for management of suspected bacterial arthritis in native joints.

Methods

During a pilot period, patients presenting with symptoms suggestive of native joint bacterial arthritis were eligible for initial management with needle arthroscopy. Procedures were performed in the operating theatre or at the patient bedside in the emergency department or inpatient ward. As our primary outcome measure, it was assessed whether needle arthroscopic lavage resulted in a clear joint. In addition, the need for conversion to standard arthroscopy or arthrotomy, the need for conversion from local to general anaesthesia, complications and the need for additional surgical intervention at follow-up during admission were recorded.

Results

Eleven joints in 10 patients (four males, age range 35 – 77) were managed with needle arthroscopy. Needle arthroscopic lavage resulted in a clear joint in all cases. Conversion to standard arthroscopy or arthrotomy was not needed. Seven procedures were performed at the patient bedside using local anaesthesia. These procedures were well tolerated and conversion to general or spinal anaesthesia was not required. There were no procedure complications. One patient received multiple needle arthroscopic lavages. No further surgical interventions beside the initial needle arthroscopic lavage were required for successful management in other cases.

Conclusions

Needle arthroscopy can be a feasible tool in the initial management of complaints suggestive for native joint bacterial arthritis, providing an effective, quick and well-tolerable intervention in the operating theatre or at the patient bedside, with the potential to relief health systems from need for scarce operating theatre time.
Linkages between market orientation and brand performance with positioning strategies of significant fashion apparels in Pakistan
Authors: Gul Rana Faizan , Liu Dunnan , Jamil Khalid , Baig Sajjad Ahmad , Awan Fazal Hussain , Liu Mingguang
Published: August 2021

The study explores the importance of market orientation strategy to enhance brand performance and the mediating role of positioning strategies. The researcher used questionnaires to collect data from the managers of middle and high fashion apparel manufacturing firms based on the quantitative research approach. The data was collected from 220 managers who were directly involved in the decision-making process. The analysis has revealed a significant impact of market orientation strategy on Pakistan’s fashion brands' performance, with the mediating effect of positioning strategies. The management of firms must give considerable importance to market orientation strategies to enhance overall brand performance. The market orientation strategies’ development is also helpful in building different positioning strategies through which performance gets enhanced. This study contributes valuable literature because it focuses on the fashion apparel industry's context, which is almost most important for everyone in the present era. Firms can focus on tight product quality control, innovative manufacturing processes, trained and experienced personnel, and extensive customer service.
Experimental infectious challenge in pigs leads to elevated fecal calprotectin levels following colitis, but not enteritis
Authors: Barbosa Jéssica A. , Rodrigues Lucas A. , Columbus Daniel A. , Aguirre Juan C. P. , Harding John C. S. , Cantarelli Vinícius S. , Costa Matheus de O.
Published: August 2021

Background

Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs.

Results

Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method.

Conclusions

Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.
Primary breast edema on contrast-enhanced digital mammography: a preliminary experience
Authors: Haggag Marwa A. , Hamed Soha T. , Mawas Aya Sedky Abd El Latif
Published: August 2021

Background

Primary breast edema can cause marked increase in skin thickness, breast density and echogenicity due to dense breast tissue filled with fluid and so causes subsequent significant attenuation of both the x-ray and ultrasound beams. The study aim is to assess the value of contrast-enhanced digital mammography (CEDM) in assessment and characterization of the obscured underlying breast lesions in cases of primary breast edema.

Results

Fifty five female participants were evaluated, of median age 51 years old and IQR 21. CEDM shows high sensitivity and specificity in the lesion detection as well as local extension delineation in cases associated with primary breast edema. It was accurate in detection of multifocal/multi-centric disease. CEDM is considered as a good negative test in cases of metastatic axillary lymph nodes to exclude and assess any associated obscured breast lesions, as it is good in delineating breast masses obscured by condensed parenchymal tissue. The calculated sensitivity of DM & CEDM was 87.5%, 95.8%, specificity was 55.5%, 72%, the PPV and NPV were 91, 93.6% and 45%, 77.8%, respectively.

Conclusions

CEDM has an important additional diagnostic value in the assessment, characterization and better delineation of breast lesions in primary edematous breast cases.
De-implementing and sustaining an intervention to eliminate nursing home resident bed and chair alarms: interviews on leadership and staff perspectives
Authors: Hartmann Christine W. , Gillespie Christopher , Sayre George G. , Snow A. Lynn
Published: August 2021

Background

Improving nursing home quality of care relies partly on reducing or stopping ineffective or harmful practices, a process known as de-implementation. We know little about de-implementation in this setting. Relatively recent policy changes reclassified resident position-change (bed and chair) alarms, which monitor resident movement, as restraints. This created an optimal environment in which to study impressions of an alarm de-implementation and sustainment intervention.

Methods

This cross-sectional interview study focused on understanding participants’ experience of a quality improvement program in the Department of Veterans Affairs Community Living Centers (nursing homes). The program’s goal was to improve resident outcomes and staff communication and teamwork through, among other foci, eliminating resident position-change alarms. The Community Living Centers were located in geographically dispersed areas of the continental United States. Interview participants were leadership and staff members from seven Community Living Centers. We conducted in-depth, semi-structured qualitative interviews using a convenience sample and used a thematic analytic approach.

Results

We conducted seventeen interviews. We identified five main themes: Initiating De-implementation (compelling participants with evidence, engaging local leadership, and site-level education and training), Changing Expectations (educating staff and family members), Using Contrasting Approaches (gradual or abrupt elimination of alarms), Witnessing Positive Effects of De-implementation (reduction in resident falls, improved resident sleep, reduction in distressing behaviors, and increased resident engagement), and Staying the Course (sustainment of the initiative).

Conclusions

Findings highlight how participants overcame barriers and successfully eliminated resident position-change alarms and sustained the de-implementation through using convincing evidence for the initiative, local leadership involvement and support, and staff and family member education and engagement. These findings and the resulting three-phase process to support nursing homes' de-implementation efforts expand the de-implementation science knowledge base and provide a promising framework for other nursing home-based de-implementation initiatives.
Amplitude variation with offset analysis of nonbright spots for gas channel identification: A case study from the western Sichuan Basin, China
Authors: Tan Feng , Cao Jun-Xing , Wang Xing-Jian , Bai Peng , Liu Jun , You Jia-Chun
Published: August 2021

The Shaximiao Formation in the Zhongjiang Gas Field of the Sichuan Basin was initially a high-productivity gas field with the bright spot channel as the vital exploration target. With further development, gas wells were obtained in some nonbright spot areas, which caused interpreters to pay great attention to the channels with nonbright spot abnormal amplitudes. We have developed a method to delineate nonbright spot channels from the complicated sand-mudstone contact relationship. First, we classified sandstone into types I, IIa, IIb, and III, depending on the responses of the amplitude variation with offset from the drilled data, to produce a forward model. We the explain why the hidden channel cannot be identified using the full-angle stack seismic data based on this model. Afterward, we put forward a difference, between the synthetic seismogram responses of bright and nonbright channels, in creating seismic-to-well ties for nonbright channels. This difference from bright channels is that the synthetic data’s wave peak is not corresponding to the peak of the real seismic data. The wave trough has the same situation. Finally, we used far-angle stack seismic data to calculate coherent energy and instantaneous spectral attributes (the latter produced for red-green-blue blending) to identify the hidden channel. We observed that parts of the channel are more clearly visible in the far-angle stack than in the full-angle stack data. In the latter situation, we cannot describe the geometric shape of the channel elaborately. The Shaximiao Formation example is a relatively effective analog for nonbright spot plays compared with elsewhere.