bluuebunny/crossref_metadata_2025 huggingface dataset:
Length doesn’t play a role – Sexual activity in men after short stem Total hip Arthroplasty
Authors: Navas Luis , Hauschild Matthias , Miehlke Wolfgang , Schmidt Sebastian , Streit Marcus , Kinkel Stefan , Zimmerer Alexander
Published: July 2022

Background

Chronic hip pain due to osteoarthritis or hip dysplasia has been shown to negatively affect many daily life aspects. One aspect, however, which persists underestimated is sexual health. The number of total hip arthroplasties (THA) are increasing, especially in young patients who have high functional expectations, not only to pain relief, but to an increase in hip mobility and quality of life as well as sexual activity.

Aim

(1) to report the demographic factors, (2) the sexual activity before and after THA, as well as the concerns related to sexual activity after THA and (3) the patient-reported outcome measurements (PROMs) in sexually active male patients.

Methods

We evaluated the results of patients between 18 and 65 years of age following primary cementless short femoral stem THA using a direct anterior approach (DAA) at a midterm follow-up of 4 years. A web-based questionnaire (via SurveyMonkey) was chosen to assess frequency, positions, complaints, fears, dealing with the questions and PROMs. Our patients sexual activity was via The Sexual Health Inventory for Men (SHIM) validated.

Results

Patients resumed their sexual activities after 6 weeks. The two main causes of difficulty in sexual activity before surgery were pain and limitation of the range of motion of the hip joint. Patients experienced less pain and an improvement in hip range of motion after THA. 89% of patients expressed a desire for more detailed and specific information on the subject. The patients foremost concern about muscle weakness, surgical scar or fear of dislocation. After 4 years follow-up our patients presented a significant improvement of the modified Harris Hip Score (mHHS) from 34.1 preoperative to 92.6 after THA.

Conclusion

THA improves the quality in sexual life, in relation to less pain and improvement in the range of motion, but not in the frequency of sexual activity. Men’s sexual positions required less mobility and could therefore be considered safer.
The impact of sex on blood pressure and anthropometry trajectories from early adulthood in a Nigerian population: insights into women’s cardiovascular disease risk across the lifespan
Authors: Adegoke Oluseyi , Ojo Oluwadamilola O. , Ozoh Obianuju B. , Akinkugbe Ayesha O. , Odeniyi Ifedayo A. , Bello Babawale T. , Agabi Osigwe P. , Okubadejo Njideka U.
Published: July 2022

Background

Sex disparities in blood pressure and anthropometry may account for differences in cardiovascular (CV) risk burden with advancing age; modulated by ethnic variability. We explored trajectories of blood pressures (BPs) and anthropometric indices with age on the basis of sex in an urban Nigerian population.

Methods

We conducted a secondary analysis on data from 5135 participants (aged 16–92 years; 2671(52%) females) from our population-based cross-sectional study of BP profiles. We utilized the WHO STEPS and standardized methods for documenting BPs, body mass index (BMI) and waist circumference (WC). Data was analyzed using Analysis of variance (ANOVA), Spearman correlation analysis and mean difference in variables (with 95% confidence interval). We explored the influence of age and sex on BP profiles and specific anthropometric indices using generalized regression analysis.

Results

In those aged 15–44 years, males had significantly higher systolic BP (SBP) and pulse pressure (PP). However, mean SBP and PP rose more steeply in females from 25 to 34 years, intersected with that of males from 45 to 54 years and remained consistently higher. Difference in mean BPs (95% Confidence Interval) (comparing < and > 45 years) was higher in females compared to males for SBP (17.4 (15.8 to 19.0) v. 9.2 (7.7 to 10.7), DBP (9.0 (7.9 to 10.1) v. 7.8 (6.7 to 8.9)), and PP (8.4 (7.3 to 9.5) v. 1.4 (0.3 to 2.5)). Females had significantly higher BMI and WC across all age groups (p < 0.001). Age more significantly correlated with BPs, BMI and WC in females. Interaction models revealed that SBP was significantly predicted by age category in females from (15–54 years), while DBP was only significantly predicted by age in the 15–34-year category (p < 0.01). BMI and WC were significantly predicted by age only in the 25–34-year category in females, (p < 0.01).

Conclusions

Our population demonstrates sex disparity in trajectories of SBP, PP, BMI and WC with age; with steeper rise in females. There is a need to focus on CV risk reduction in females, starting before, or during early adulthood.
Open Doors by Fair Means: a quasi-experimental controlled study on the effects of an open-door policy on acute psychiatric wards
Authors: Schreiber Lisa K. , Metzger Florian G. , Flammer Erich , Rinke Heike , Fallgatter Andreas J. , Steinert Tilman
Published: July 2022

Background

Psychiatric wards treating involuntarily admitted patients are traditionally locked to prevent absconding. However, on the basis of observational evidence, the necessity for locked units in psychiatric hospitals has increasingly been questioned. Updated Mental Health Laws in several Federal States of Germany legitimate involuntary commitment without generally locked doors.

Methods

We examined the effects of an open-door policy in a quasi-experimental, prospective design. For the first time, at each of two locations, two identical wards serving as control and intervention could be compared. After a baseline period of three months, one ward at each location started the 12 month intervention period with the implementation of an open-door policy, while the respective control ward, as before, used open doors only facultatively. Primary outcomes were average opening times of the four wards between 8 a.m. and 8 p.m., and the number of involuntary treatment days with the doors open. Secondary outcomes were adverse events including aggressive incidents, absconding, suicide attempts and coercive measures.

Results

Overall, door-opening times increased significantly at both sites´ intervention wards. The number of adverse events did not increase during intervention period. Frequencies of coercive measures decreased in Friedrichshafen and remained unchanged in Tuebingen. In case of the intervention ward in Friedrichshafen, doors were open in up to 91% of all involuntary treatment days, whereas in the control ward, this was only the case in 67% of all involuntary treatment days (p < .001). In case of the intervention ward in Tuebingen, 45% of involuntary treatment days had open doors, compared to 30% in the control ward (p < .001).

Conclusions

It is possible to manage psychiatric wards with open doors without taking inappropriate risks. The extent to which open-door policies are achievable is be dependent on staffing and patient characteristics. Further research is necessary to explore the role of staff attitudes.

Trial registration

Our trial "Open Doors by Fair Means" is retrospectively registered with DRKS (DRKS00015154) on Sept. 10th 2018 and displayed on the public web site. It is searchable via its meta-registry (http://apps.who.int/trialsearch/).
Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial–mesenchymal transition
Authors: Sun Hongyan , Zhang Chuan , Zheng Yang , Liu Chenlu , Wang Xue , Cong Xianling
Published: July 2022

Background

Glutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored.

Methods

A total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial–mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism.

Results

A decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = − 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process.

Conclusions

This study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.
The recombinant Erns and truncated E2-based indirect enzyme-linked immunosorbent assays to distinguishably test specific antibodies against classical swine fever virus and bovine viral diarrhea virus
Authors: Yi Weicheng , Zhu Hongchang , Wu Yihan , Li Qingmei , Lou Wange , Zhao Haizhong , Pan Zishu
Published: July 2022

Background

Classical swine fever (CSF) virus is the causative agent of an economically important, highly contagious disease of pigs. CSFV is genetically and serologically related to bovine viral diarrhea virus (BVDV). BVDV infection in pigs can mimic CSF clinical signs, which cause difficulty in differentiation. Serological test for detection of virus specific antibodies is a valuable tool for diagnosis and surveillance of CSFV and BVDV infections in animals. The aim of this study was to develop the CSFV Erns and BVDV tE2 -based ELISAs to distinguishably test specific antibodies against CSFV and BVDV.

Methods

The CSFV Erns and truncated E2 (tE2, residues 690–865) of BVDV were expressed in E. coli and purified by Ni–NTA affinity chromatography, respectively. Employing Erns or tE2 protein as diagnostic antigen, indirect ELISAs were developed to distinguishably test specific antibodies against CSFV and BVDV. The specificity and sensitivity of ELISAs were evaluated using a panel of virus specific sera of pigs, immunized rabbits and immunized mice. A total 150 clinical serum samples from farm pigs were measured by the developed ELISAs and compared with virus neutralizing test (VNT).

Results

Indirect ELISA was established based on recombinant CSFV Erns or BVDV tE2 protein, respectively. No serological cross-reaction between antibodies against CSFV and BVDV was observed in sera of immunized rabbits, immunized mice or farm pigs by detections of the Erns and tE2 -based ELISAs. Compared to VNT, the CSFV Erns -based ELISA displayed a high sensitivity (93.3%), specificity (92.0%) and agreement rate (92.7%), and the sensitivity, specificity and agreement rate of BVDV tE2 -based ELISA was 92.3%, 95.2% and 94.7%, respectively.

Conclusion

The newly developed ELISAs are highly specific and sensitive and would be valuable tools for serological diagnosis for CSFV and BVDV infections.
Single session therapy in pediatric healthcare: the value of adopting a strengths-based approach for families living with neurological disorders
Authors: Mulligan Janice , Olivieri Heather , Young Katarina , Lin Jia , Anthony Samantha J.
Published: July 2022

Background

Pediatric patients with neurological disorders often require lifelong management of symptoms and behaviours that can result in enduring emotional burden, stress and impacted health-related quality of life. Single session therapy (SST) draws upon patients’ existing skills and knowledge and has emerged as a therapeutic approach to address pediatric patient and family needs in a timely manner. This study aimed to assess the clinical effectiveness of SST for pediatric patients with neurological disorders and their families, considering self-efficacy, distress, anxiety, therapeutic alliance and client satisfaction, as well as perceptions of whether SST met their pressing needs.

Methods

A convergent parallel mixed-methods design included quantitative data collection via five standardized questionnaires across three time points and qualitative data collection through semi-structured interviews. Quantitative and qualitative data were analyzed independently and then integrated.

Results

The study comprised of 135 participants, including patients, parents and siblings across diverse neurological conditions. Scores of self-efficacy and anxiety in children, and distress and anxiety in adults, improved significantly after the SST. Notably, changes in anxiety in adults remained significant five to seven weeks after the SST. Seventeen participants participated in 12 semi-structured interviews. Participants described that SST (1) was a missing piece in ongoing clinical care, (2) illuminated existing strengths and resilience, and (3) effected a lasting impact beyond the single session.

Conclusions

SST may be a promising initial, strengths-based treatment to support the short-term and potentially long-term needs of pediatric patients with neurological disorders and their families by emphasizing existing strengths, supporting therapeutic alliance and cultivating hope.
Sporadic medullary thyroid cancer: a systematic review and meta-analysis of clinico-pathological and mutational characteristics predicting recurrence
Authors: Cosway Benjamin , Fussey Jonathan , Kim Dae , Wykes James , Elliott Michael , Smith Joel
Published: July 2022

Introduction

Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet there is little evidence to support risk stratification of patients according to risk of recurrence.

Methods

A systematic review and meta-analysis was performed investigating clinical and pathological factors that are associated with recurrent disease in patients with medullary thyroid cancer.

Results

10 studies totalling 458 patients were included in the meta-analyses. T3 and T4 disease (OR 9.33 (95% CI 2.5 – 34.82) p = 0.0009.), AJCC stage III and IV disease (OR 13.34 (95% CI 2.9 – 60.3) p = 0.0008) and the presence of nodal disease (OR 7.28 (95% CI 7.2–43.3) p = 0.03) were all associated with recurrent disease. RET mutations (OR 0.08 (95% CI -0.03–0.19) p = 0.17) and RET 918 T mutations (OR 1.77 (95% CI 0.804.0) P = 0.17) were not associated with disease recurrence. It was not possible to pool data with respect to extrathyroidal extension, extracapsular extension, peri-neural and lymphovascular invasion and RAS mutations.

Conclusion

T3 and T4 disease, AJCC stage III and IV disease and the presence of nodal disease are associated with recurrent disease. The heterogeneous reporting of recurrence and the lack of individual patient data precludes larger scale meta-analyses. Future research in this area should involve collaboration to establish standardised definitions of disease recurrence.
PM2.5 promotes NSCLC carcinogenesis through translationally and transcriptionally activating DLAT-mediated glycolysis reprograming
Authors: Chen Qianqian , Wang Yiling , Yang Lin , Sun Liyuan , Wen Yuxin , Huang Yongyi , Gao Kaiping , Yang Wenhan , Bai Feng , Ling Lijuan , Zhou Zizi , Zhang Xiaoming , Xiong Juan , Zhai Rihong
Published: July 2022

Background

Airborne fine particulate matter (PM2.5) has been associated with lung cancer development and progression in never smokers. However, the molecular mechanisms underlying PM2.5-induced lung cancer remain largely unknown. The aim of this study was to explore the mechanisms by which PM2.5 regulated the carcinogenesis of non-small cell lung cancer (NSCLC).

Methods

Paralleled ribosome sequencing (Ribo-seq) and RNA sequencing (RNA-seq) were performed to identify PM2.5-associated genes for further study. Quantitative real time-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC) were used to determine mRNA and protein expression levels in tissues and cells. The biological roles of PM2.5 and PM2.5-dysregulated gene were assessed by gain- and loss-of-function experiments, biochemical analyses, and Seahorse XF glycolysis stress assays. Human tissue microarray analysis and 18F-FDG PET/CT scans in patients with NSCLC were used to verify the experimental findings. Polysome fractionation experiments, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assay were implemented to explore the molecular mechanisms.

Results

We found that PM2.5 induced a translation shift towards glycolysis pathway genes and increased glycolysis metabolism, as evidenced by increased L-lactate and pyruvate concentrations or higher extracellular acidification rate (ECAR) in vitro and in vivo. Particularly, PM2.5 enhanced the expression of glycolytic gene DLAT, which promoted glycolysis but suppressed acetyl-CoA production and enhanced the malignancy of NSCLC cells. Clinically, high expression of DLAT was positively associated with tumor size, poorer prognosis, and SUVmax values of 18F-FDG-PET/CT scans in patients with NSCLC. Mechanistically, PM2.5 activated eIF4E, consequently up-regulating the expression level of DLAT in polysomes. PM2.5 also stimulated transcription factor Sp1, which further augmented transcription activity of DLAT promoter.

Conclusions

This study demonstrated that PM2.5-activated overexpression of DLAT and enhancement in glycolysis metabolism contributed to the tumorigenesis of NSCLC, suggesting that DLAT-associated pathway may be a therapeutic target for NSCLC.
ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42
Authors: Zhang Xin , Ren Liangliang , Wu Junhua , Feng Rongni , Chen Yunyang , Li Ronggang , Wu Meimei , Zheng Mingzhu , Wu Xing Gui , Luo Wanjun , He Hongle , Huang Yanming , Tang Miaoling , Li Jun
Published: July 2022

Background

The extravasation capability of hepatocellular carcinoma (HCC) cells plays a vital role in distant metastasis. However, the underlying mechanism of extravasation in HCC lung metastasis remains largely unclear.

Methods

The expression of ARHGEF37 in human HCC specimens and HCC cell lines was examined by quantitative RT-PCR, western blot, and immunohistochemistry (IHC) analyses. The biological roles and mechanisms of ARHGEF37/Cdc42 in promoting lung metastasis were investigated in vitro and in vivo using cell lines, patient samples, xenograft models.

Results

In the current study, we found that Rho guanine nucleotide exchange factor 37 (ARHGEF37) was upregulated in human HCC samples and was associated with tumor invasiveness, pulmonary metastasis and poor prognosis. Overexpressing ARHGEF37 significantly enhanced the extravasation and metastatic capability of HCC cells via facilitating tumor cell adhesion to endothelial cells and trans-endothelial migration. Mechanistically, ARHGEF37 directly interacted with and activated Cdc42 to promote the invadopodia formation in HCC cells, which consequently disrupted the interaction between endothelial cells and pericytes. Importantly, treatment with ZCL278, a specific inhibitor of Cdc42, dramatically inhibited the attachment of ARHGEF37-overexpressing HCC cells to endothelial cells, and the adherence and extravasation in the lung alveoli, resulting in suppression of lung metastasis in mice.

Conclusion

Our findings provide a new insight into the underlying mechanisms on the ARHGEF37 overexpression-mediated extravasation and pulmonary metastasis of HCC cells, and provided a potential therapeutic target for the prevention and treatment of HCC pulmonary metastasis.
Senescence in osteoarthritis: from mechanism to potential treatment
Authors: Liu Yikai , Zhang Zian , Li Tao , Xu Hao , Zhang Haining
Published: July 2022

Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Increased numbers of senescent chondrocytes are found in OA cartilage. Selective clearance of senescent chondrocytes in a post-traumatic osteoarthritis (PTOA) mouse model ameliorated OA development, while intraarticular injection of senescent cells induced mouse OA. However, the means and extent to which senescence affects OA remain unclear. Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. Natural killer (NK) cells participate in the elimination of senescent cells in multiple organs. A relatively comprehensive discussion is presented in that section. Risk factors for OA are ageing, obesity, metabolic disorders and mechanical overload. Determining the relationship between known risk factors and senescence will help elucidate OA pathogenesis and identify optimal treatments.
Neutrophil extracellular traps promote thrombogenicity in cerebral venous sinus thrombosis
Authors: Jin Jiaqi , Qiao Shan , Liu Jie , Li Wenqiang , Wang Fang , Gao Xin , Tian Jiawei , Wang Nan , Zhang Jiheng , Dong Jiawei , li Haiyun , Wang Jianjun , Hu Shaoshan , Zhou Peng
Published: July 2022

Background

Neutrophil extracellular traps (NETs) contribute to the creation of a coagulation state in various diseases. Currently, it is not clear whether NETs are present in the thrombi and plasma of patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the presence of NETs in thrombi and blood samples from CVST patients and the procoagulant activity (PCA) of NETs during the progression of CVST.

Results

Thrombi obtained from CVST patients undergoing thrombectomy were examined by immunochemistry using neutrophil elastase (NE), CD66b and citrullinated histone H3(citH3). The presence of NET markers in samples from 37 CVST patients and 32 healthy people was evaluated by ELISA. NET-producing neutrophils and neutrophil-platelet (PLT) aggregates were examined in samples obtained from CVST patients and healthy people by flow cytometry. The TAT complex in plasma sample from each group was detected by ELISA to evaluate the procoagulant activity of NETs in CVST patients. Neutrophils from healthy subjects were treated with PLT-rich plasma in the presence of anti-PF4 antibodies or an autophagy inhibitor and analyzed by flow cytometry and confocal microscopy. After treatment with NETs, the expression of von Willebrand factor (VWF), tissue factor (TF) and CD31 in human brain microvascular endothelial cells (HBMECs) was measured by confocal microscopy and western blotting. Our results showed that NETs were abundant in the plasma and thrombi from CVST patients. Platelet factor 4 (PF4) from CVST PLTs induced NET generation through autophagy. NETs could induce PCA by modulating TF and phosphatidylserine (PS) in CVST. NETs also disrupted the endothelial barrier and transformed ECs into a procoagulant phenotype to exacerbate thrombogenicity.

Conclusions

NET generation was mediated by PF4 from PLTs through autophagy and contribute to thrombosis in CVST patients.
RH simulation model for canvas paintings protected by an aluminium backplate and an additional hygroscopic layer
Authors: Ferrer Santi , Campo-Francés Gema , Grau-Bové Josep , Bautista-Morenilla Iris , Nualart-Torroja Anna
Published: July 2022

To protect a canvas easel painting, a common conservation strategy is to add a back plate at the stretcher, creating a closed air void. This plate protects not only from dust but mainly from temperature and relative humidity (RH) variations in the room and moisture changes in the wall on which it is hanging. The addition of hygroscopic layers can reduce the amplitude and change phase of humidity oscillations. This paper proposes a new mathematical model that can be used to predict moisture levels within the canvas when this conservation strategy is applied. The model is compared against the temperature and RH detailed experimental data, captured and shown in the latest paper by Padfield et al. Back protection of canvas painting. Our paper presents values of T, RH and mixing ratio (MR) obtained at the different layers of an easel painting, protected and unprotected, with cotton and without it, submitted to different room and wall temperature and RH cycles. The experimental results show a phase displacement between the canvas temperatures and the corresponding RH values in the canvas air boundary layer. In some cases this phase shift, which is an unexpected behaviour, allows RH and temperatures to achieve their maximum value at the same time. The purpose of the model is to simulate the RH response at the different air boundary layers inside the air void, such as the canvas, the aluminium back plate, and the hygroscopic cotton protection, produced by cyclic variations of temperature in the room or the wall. The model is built simulating four interrelated processes: the canvas permeation flow, the air infiltration rate between room and void, the equilibrium moisture content (EMC) and the vapour sorption rate for the canvas and the cotton. A key innovation of the model is the dependence between EMC, sorption rate, and RH condition, which captures the counter-intuitive behaviours observed in the data. The model results agree with the experimental results. The developed tool allows the interpretation of the processes involved and to extend the simulations to other cases, materials, and conditions.
Efficient management of the nitritation-anammox microbiome through intermittent aeration: absence of the NOB guild and expansion and diversity of the NOx reducing guild suggests a highly reticulated nitrogen cycle
Authors: Palomo Alejandro , Azevedo Daniela , Touceda-Suárez María , Domingo-Félez Carlos , Mutlu A. Gizem , Dechesne Arnaud , Wang Yulin , Zhang Tong , Smets Barth F.
Published: July 2022

Obtaining efficient autotrophic ammonia removal (akapartial nitritation-anammox, or PNA) requires a balanced microbiome with abundant aerobic and anaerobic ammonia oxidizing bacteria and scarce nitrite oxidizing bacteria. Here, we analyzed the microbiome of an efficient PNA process that was obtained by sequential feeding and periodic aeration. The genomes of the dominant community members were inferred from metagenomes obtained over a 6 month period. ThreeBrocadiaspp. genomes and threeNitrosomonasspp. genomes dominated the autotrophic community; no NOB genomes were retrieved. Two of theBrocadiaspp. genomes lacked the genomic potential for nitrite reduction. A diverse set of heterotrophic genomes was retrieved, each with genomic potential for only a fraction of the denitrification pathway. A mutual dependency in amino acid and vitamin synthesis was noted between autotrophic and heterotrophic community members. Our analysis suggests a highly-reticulated nitrogen cycle in the examined PNA microbiome with nitric oxide exchange between the heterotrophs and the anammox guild.
Proteomic, mechanical, and biochemical development of tissue-engineered neocartilage
Authors: Bielajew Benjamin J. , Donahue Ryan P. , Lamkin Elliott K. , Hu Jerry C. , Hascall Vincent C. , Athanasiou Kyriacos A.
Published: July 2022

Background

The self-assembling process of cartilage tissue engineering is a promising technique to heal cartilage defects, preventing osteoarthritic changes. Given that chondrocytes dedifferentiate when expanded, it is not known if cellular expansion affects the development of self-assembled neocartilage. The objective of this study was to use proteomic, mechanical, and biochemical analyses to quantitatively investigate the development of self-assembled neocartilage derived from passaged, rejuvenated costal chondrocytes.

Methods

Yucatan minipig costal chondrocytes were used to create self-assembled neocartilage constructs. After 1, 4, 7, 14, 28, 56, or 84 days of self-assembly, constructs were analyzed through a variety of histological, biomechanical, biochemical, and proteomic techniques.

Results

It was found that temporal trends in neocartilage formation are similar to those seen in native hyaline articular cartilage development. For example, between days 7 and 84 of culture, tensile Young’s modulus increased 4.4-times, total collagen increased 2.7-times, DNA content decreased 69.3%, collagen type II increased 1.5-times, and aggrecan dropped 55.3%, mirroring trends shown in native knee cartilage. Importantly, collagen type X, which is associated with cartilage calcification, remained at low levels (≤ 0.05%) at all neocartilage developmental time points, similar to knee cartilage (< 0.01%) and unlike donor rib cartilage (0.98%).

Conclusions

In this work, bottom-up proteomics, a powerful tool to interrogate tissue composition, was used for the first time to quantify and compare the proteome of a developing engineered tissue to a recipient tissue. Furthermore, it was shown that self-assembled, costal chondrocyte-derived neocartilage is suitable for a non-homologous approach in the knee.
Toward a more comprehensive modeling of sequential lineups
Authors: Kellen David , McAdoo Ryan M.
Published: July 2022

Sequential lineups are one of the most commonly used procedures in police departments across the USA. Although this procedure has been the target of much experimental research, there has been comparatively little work formally modeling it, especially the sequential nature of the judgments that it elicits. There are also important gaps in our understanding of how informative different types of judgments can be (binary responses vs. confidence ratings), and the severity of the inferential risks incurred when relying on different aggregate data structures. Couched in a signal detection theory (SDT) framework, the present work directly addresses these issues through a reanalysis of previously published data alongside model simulations. Model comparison results show that SDT modeling can provide elegant characterizations of extant data, despite some discrepancies across studies, which we attempt to address. Additional analyses compare the merits of sequential lineups (with and without a stopping rule) relative to showups and delineate the conditions in which distinct modeling approaches can be informative. Finally, we identify critical issues with the removal of the stopping rule from sequential lineups as an approach to capture within-subject differences and sidestep the risk of aggregation biases.
Vitamin D supplementation modulates autophagy in the pristane-induced lupus model
Authors: dos Santos Manuela , de Souza Silva Jordana Miranda , Bartikoski Bárbara Jonson , Freitas Eduarda Correa , Busatto Amanda , do Espírito Santo Rafaela Cavalheiro , Monticielo Odirlei Andre , Xavier Ricardo Machado
Published: July 2022

Introduction/objectives

Clinical evidence of skeletal muscle involvement is not uncommon in systemic lupus erythematosus (SLE). Because of the poor understanding of signaling pathways involved in SLE muscle wasting, the  aim of this study was to evaluate the effects of vitamin D supplementation on skeletal muscle in mice with pristane-induced lupus.

Methods

Balb/c mice with lupus-like disease induced by pristane injection were randomized into three groups: pristane-induced lupus (PIL; n = 10), pristane-induced lupus + vitamin D supplementation (PIL + VD; n = 10) and healthy controls (CO; n = 8). Physical function was evaluated on days 0, 60, 120 and 180. The tibialis anterior and gastrocnemius muscles were collected to evaluate myofiber cross-sectional area (CSA) and protein expression.

Results

The PIL + VD group showed lower muscle strength compared to the CO and PIL groups at different time points. PIL mice showed similar myofiber CSA compared to CO and PIL + VD groups. LC3-II expression was higher in PIL compared to CO and PIL + VD groups. MyoD expression was higher in PIL mice compared to PIL + VD, while myostatin expression was higher in PIL + VD than PIL group. Myogenin expression levels were decreased in the PIL + VD group compared with the CO group. The Akt, p62 and MuRF expressions and mobility assessment showed no significance.

Conclusions

Changes in skeletal muscle in PIL model happen before CSA reduction, possibly due to autophagy degradation, and treatment with Vitamin D has a impact on physical function by decreasing muscle strength and time of fatigue.. Vitamin D supplementation has a potential role modulating physical parameters and signaling pathways in muscle during pristane-induced lupus model.
Diffusion-weighted magnetic resonance imaging in differentiation between different vertebral lesions using ADC mapping as a quantitative assessment tool
Authors: Allam Khaled Essmat , Abd Elkhalek Yasser Ibrahim , Hassan Hend Galal Eldeen Mohamed Ali , Emara Mostafa Abd Elhalim
Published: July 2022

Background

Diffusion-weighted imaging is one of the most useful clinical MRI techniques. Including this technique with other sequences used for routine spine scanning improves sensitivity and the capacity to characterize lesions. This study aims to evaluate the utility of apparent diffusion coefficient obtained from diffusion-weighted MR imaging in differentiating between benign and malignant vertebral lesions according to the optimal cutoff ADC value.

Results

This study included 30 patients at Ain Shams University hospitals; all of them were subjected to full clinical assessment and magnetic resonance imaging. Patients were classified into 4 groups: inflammatory lesions (12 cases) followed by malignant lesions (7 cases), then benign neoplastic lesions (6 cases), then traumatic lesions (3 cases) and osteoporosis (two cases). Inflammatory lesions revealed restricted diffusion. Benign neoplastic lesions/hemangioma showed low signal at DWIs due to free diffusion, while malignant/metastatic lesions showed restricted diffusion. Traumatic lesions showed restricted diffusion. The osteoporotic lesions showed iso- to hyper-intense signal at DWIs. The mean ADC value of the benign lesions was 1.8 ± 0.43 mm2/s, while metastatic tumors was 0.96 ± 0.5 × 10–3 mm2/s; however, overlapping values may be present.

Conclusions

Compared with benign tumors, malignant tumors have lower ADC values; nevertheless, some lesions, such as tuberculosis, have low ADC values that are like those of malignant tumors. Diffusion MRI and ADC values should always be analyzed in conjunction with standard MRI sequences as well as a thorough clinical history and examination.
Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study
Authors: Ossa Gomez Carlos Andrés , Achatz Maria Isabel , Hurtado Mabel , Sanabria-Salas María Carolina , Sullcahuaman Yasser , Chávarri-Guerra Yanin , Dutil Julie , Nielsen Sarah M. , Esplin Edward D. , Michalski Scott T. , Bristow Sara L. , Hatchell Kathryn E. , Nussbaum Robert L. , Pineda-Alvarez Daniel E. , Ashton-Prolla Patricia
Published: July 2022

PURPOSE

To report on pathogenic germline variants detected among individuals undergoing genetic testing for hereditary breast and/or ovarian cancer (HBOC) from Latin America and compare them with self-reported Hispanic individuals from the United States.

METHODS

In this cross-sectional study, unrelated individuals with a personal/family history suggestive of HBOC who received clinician-ordered germline multigene sequencing were grouped according to the location of the ordering physician: group A, Mexico, Central America, and the Caribbean; group B, South America; and group C, United States with individuals who self-reported Hispanic ethnicity. Relatives who underwent cascade testing were analyzed separately.

RESULTS

Among 24,075 unrelated probands across all regions, most were female (94.9%) and reported a personal history suggestive of HBOC (range, 65.0%-80.6%); the mean age at testing was 49.1 ± 13.1 years. The average number of genes analyzed per patient was highest in group A (A 63 ± 28, B 56 ± 29, and C 40 ± 28). Between 9.1% and 18.7% of patients had pathogenic germline variants in HBOC genes (highest yield in group A), with the majority associated with high HBOC risk. Compared with US Hispanics individuals the overall yield was significantly higher in both Latin American regions (A v C P = 1.64×10–9, B v C P < 2.2×10–16). Rates of variants of uncertain significance were similar across all three regions (33.7%-42.6%). Cascade testing uptake was low in all regions (A 6.6%, B 4.5%, and C 1.9%).

CONCLUSION

This study highlights the importance of multigene panel testing in Latin American individuals with newly diagnosed or history of HBOC, who can benefit from medical management changes including targeted therapies, eligibility to clinical trials, risk-reducing surgeries, surveillance and prevention of secondary malignancy, and genetic counseling and subsequent cascade testing of at-risk relatives.
Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH): A Multicenter, Open-Label, Randomized, Phase II Trial
Authors: Fornecker Luc-Matthieu , Lazarovici Julien , Aurer Igor , Casasnovas René-Olivier , Gac Anne-Claire , Bonnet Christophe , Bouabdallah Krimo , Feugier Pierre , Specht Lena , Molina Lysiane , Touati Mohamed , Borel Cécile , Stamatoullas Aspasia , Nicolas-Virelizier Emmanuelle , Pascal Laurent , Lugtenburg Pieternella , Di Renzo Nicola , Vander Borght Thierry , Traverse-Glehen Alexandra , Dartigues Peggy , Hutchings Martin , Versari Annibale , Meignan Michel , Federico Massimo , André Marc ,   for the LYSA-FIL-EORTC Intergroup
Published: July 2022

PURPOSE

The prognosis of patients with early-stage unfavorable Hodgkin lymphoma remains unsatisfactory. We assessed the efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (ClinicalTrials.gov identifier: NCT02292979 ).

METHODS

BREACH is a multicenter, randomized, open-label, phase II trial. Eligible patients were age 18-60 years with ≥ 1 unfavorable EORTC/LYSA criterion. Patients were randomly assigned (2:1) to four cycles of BV-AVD or standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD), followed by 30 Gy involved node radiotherapy. The primary end point was the positron emission tomography (PET) response rate after two cycles by expert independent review using the Deauville score. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%. We hypothesized a 10% increase in the PET-negative rate after two cycles of BV-AVD.

RESULTS

Between March 2015 and October 2016, 170 patients were enrolled. After two cycles, the primary end point of the study was met: 93 (82.3%; 90% CI, 75.3 to 88.0) of 113 patients in the BV-AVD arm were PET-negative (Deauville score 1-3) compared with 43 (75.4%; 90% CI, 64.3% to 84.5%) of 57 in the ABVD arm. The 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9 to 99.1) and 92.6% (95% CI, 81.4% to 97.2%) in the BV-AVD and ABVD arms, respectively. High total metabolic tumor volume was associated with a significantly shorter PFS (hazard ratio, 17.9; 95% CI, 2.2 to 145.5; P < .001). For patients with high total metabolic tumor volume, the 2-year PFS rate was 90.9% (95% CI, 74.4 to 97.0) and 70.7% (95% CI, 39.4% to 87.9%) in the BV-AVD and ABVD arms, respectively.

CONCLUSION

BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.
Phase II Study of Enzalutamide for Patients With Androgen Receptor–Positive Salivary Gland Cancers (Alliance A091404)
Authors: Ho Alan L. , Foster Nathan R. , Zoroufy Alex J. , Campbell Jordan D. , Worden Francis , Price Katharine , Adkins Douglas , Bowles Daniel W. , Kang Hyunseok , Burtness Barbara , Sherman Eric , Morton Roscoe , Morris Luc G.T. , Nadeem Zaineb , Katabi Nora , Munster Pamela , Schwartz Gary K.
Published: July 2022

PURPOSE

The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC.

METHODS

Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety.

RESULTS

Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR– (6 of 13 [46.2%]) or human epidermal growth factor receptor 2–targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide.

CONCLUSION

Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.
Circulating 1,5-Anhydroglucitol as a Biomarker of ß-cell Mass Independent of a Diabetes Phenotype in Human Subjects
Authors: Jiménez-Sánchez Cecilia , Mezza Teresa , Sinturel Flore , Li Lingzi , Di Giuseppe Gianfranco , Quero Giuseppe , Jornayvaz François R , Guessous Idris , Dibner Charna , Schrauwen Patrick , Alfieri Sergio , Giaccari Andrea , Maechler Pierre
Published: July 2022

Context

During an asymptomatic prediabetic state, the functional ß-cell mass decreases to a critical threshold, triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass.

Objective

Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage. The present study investigated the putative corresponding relevance of circulating 1,5-anhydroglucitol in different human cohorts.

Methods

We analyzed clinical and blood parameters in patients with established type 2 diabetes and subjects considered at high risk of developing diabetes, as well as patients with no history of diabetes scheduled for pancreaticoduodenectomy.

Results

Circulating 1,5-anhydroglucitol was reduced in type 2 diabetic patients, negatively correlating with fasting plasma glucose (P < 0.0001) and hemoglobin A1c (P < 0.0001). In healthy subjects, 1,5-AG levels positively correlated with body mass index (P = 0.004) and Homeostatic Model Assessment of Insulin Resistance %S (P < 0.03) and was particularly high in nondiabetic obese individuals, potentially accounting for compensatory ß-cell expansion. Patients with no history of diabetes undergoing pancreaticoduodenectomy exhibited a 50% reduction of circulating 1,5-anhydroglucitol levels following surgery leading to an acute loss of their ß-cell mass (P = 0.002), regardless their glucose tolerance status.

Conclusion

In summary, plasma concentration of 1,5-anhydroglucitol follows the ß-cell mass and its noninvasive monitoring may alert about the loss of ß cells in subjects at risk for diabetes, an event that cannot be captured by other clinical parameters of glycemic control.
The Retro Superior Costotransverse Ligament Space as a New Target for Ultrasound-Guided Intertransverse Process Block: A Report of 2 Cases
Authors: Karmakar Manoj Kumar , Sivakumar Ranjith Kumar , Sheah Kenneth , Pangthipampai Pawinee , Lönnqvist Per-Arne
Published: July 2022

An intertransverse process block (ITPB) is a paraspinal thoracic nerve block technique, where the local anesthetic (LA) is injected into the thoracic intertransverse tissue complex posterior to the superior costotransverse ligament (SCTL). Although an ITPB can be ultrasound-guided, it is performed using surrogate bony landmarks without even identifying the SCTL. This report describes a transverse ultrasound imaging technique to identify the retro-SCTL space and perform an ITPB with a retro-SCTL space injection, in 2 patients undergoing video-assisted thoracoscopic surgery. The resultant bilateral, symmetrical, thoracolumbar anesthesia was consistent with epidural spread of the LA and effective for perioperative analgesia.
Is It Only a Numbers Game? A Macro-Level Study of Educational Hypogamy
Authors: Han Sinn Won
Published: July 2022

In many countries, the tendency for highly educated women to marry down in education has markedly increased. Research has pointed to an oversupply of highly educated women—that is, a marriage squeeze affecting women—as the core reason for this phenomenon. This study aims to provide a more comprehensive understanding of the causes of this marriage trend by analyzing over-time data drawn from IPUMS International census microdata samples for 34 countries. Several key findings are notable. First, the degree of educational hypogamy is associated with the magnitude of the deficit in college-educated men in the marriage market, which is consistent with the marriage squeeze hypothesis. Second, the degree of educational hypogamy is related to the economic empowerment of college-educated women, even after accounting for the mating squeeze effect. Third, counterfactual simulations show that while the mating squeeze is the major driver of educational hypogamy in the majority of the sample countries, the economic empowerment of college-educated women plays an equally important role in several countries.
The Contribution of Price Growth to Pharmaceutical Revenue Growth in the United States: Evidence from Medicines Sold in Retail Pharmacies
Authors: Kakani Pragya , Chernew Michael , Chandra Amitabh
Published: July 2022

Context: To what extent does pharmaceutical revenue growth depend on new medicines versus increasing prices for existing medicines? Moreover, does using list prices, as is commonly done, instead of prices net of confidential rebates offered by manufacturers, which are harder to observe, change the relative importance of the sources of revenue growth?

Methods: This study uses data from SSR Health LLC to address these research questions using decomposition methods that analyze list prices, prices net of rebates, and sales for branded pharmaceutical products sold primarily through retail pharmacies.

Findings: From 2009 to 2019, retail pharmaceutical revenue growth was primarily driven by new products rather than by price increases on existing products. Failing to account for confidential rebates creates a more prominent role for price increases in explaining revenue growth, because list price inflation during this period was 10.9%, whereas net price inflation was 3.3%.

Conclusions: Policies that restrict price growth on existing medicines likely need to be coupled with policies that reduce launch prices to have a meaningful long-term impact on pharmaceutical revenue growth. Using pharmaceutical list prices is often an inadequate approximation for net prices because the role of rebates has increased and varies by drug class.