bluuebunny/crossref_metadata_2025 huggingface dataset:
Can neoadjuvant chemotherapy improve survival in stage T3-4N1 nasopharyngeal carcinoma? A propensity matched analysis
Authors: Wang Lei , Wu Zheng , Xie Dehuan , Lv Shaowen , Xia Liangping , Su Yong
Published: July 2020

Background

To estimate the efficacy of neoadjuvant chemotherapy (NCT) in stage T3-4N1 nasopharyngeal carcinoma (NPC).

Methods

Data on stage T3-4N1 NPC patients treated with concurrent chemoradiotherapy (CCRT) with or without NCT at the Sun Yat-sen University Cancer Center between January 2006 and December 2013 were retrospectively reviewed. Propensity score matching (PSM) was carried out to balance prognostic factors in NCT followed by CCRT (NCT + CCRT) group and CCRT group in a 1:1 ratio. Survival outcomes of matched patients in the two groups were compared, and prognostic factors were identified using Cox regression model.

Results

A total of 282 patients were involved in this study, with 136 of NCT + CCRT group and 146 of CCRT group. After PSM, 85 pairs of patients were selected. There were no significant differences in 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and recurrence-free survival (RFS) between NCT + CCRT group and CCRT group (81.0% vs. 77.5%, P = 0.750; 85.8% vs. 88.1%, P = 0.495; 92.5% vs. 93.9%, P = 0.759; 81.0% vs.77.5%, P = 0.919, respectively). Multivariate analysis found that smoking history (P = 0.044) and T classification (P = 0.027) were independent prognostic factors for OS, lymph node diameter (P = 0.032) was independent prognostic factor for LRFS, positive pretreatment lymph node condition (PLNC), which was defined as the lymph node necrosis or confluent, was independent prognostic factor for DRFS (P = 0.007), and RFS (P = 0.009). Lower 5-year OS (82.7% vs. 94.1%, P = 0.014), DRFS (79.3% vs. 96.2%, P = 0.003), and RFS (62.4% vs. 86.8%, P = 0.001) were found in positive PLNC group compared with negative PLNC group. In terms of toxicities, the incidences of acute hematological Grade 3–4 adverse events (AEs) were higher in NCT + CCRT group compared with CCRT group (P < 0.05), while no significant difference was observed in the rates of non-hematological Grade 3–4 AEs between these two groups (P > 0.05).

Conclusions

Additional NCT is not associated with improved survival outcomes for patients with stage T3-4N1 NPC, but bring increased hematological Grade 3–4 AEs. PLNC is independent prognostic factor in stage T3-4N1 NPC, with positive PLNC correlating with poor survival outcomes.
Intraoperative post-annuloplasty three-dimensional valve analysis does not predict recurrent ischemic mitral regurgitation
Authors: Meijerink Frank , Wijdh-den Hamer Inez J. , Bouma Wobbe , Pouch Alison M. , Aly Ahmed H. , Lai Eric K. , Eperjesi Thomas J. , Acker Michael A. , Yushkevich Paul A. , Hung Judy , Mariani Massimo A. , Khabbaz Kamal R. , Gleason Thomas G. , Mahmood Feroze , Gorman Joseph H. , Gorman Robert C.
Published: July 2020

Background

High ischemic mitral regurgitation (IMR) recurrence rates continue to plague IMR repair with undersized ring annuloplasty. We have previously shown that pre-repair three-dimensional echocardiography (3DE) analysis is highly predictive of IMR recurrence. The objective of this study was to determine the quantitative change in 3DE annular and leaflet tethering parameters immediately after repair and to determine if intraoperative post-repair 3DE parameters would be able to predict IMR recurrence 6 months after repair.

Methods

Intraoperative pre- and post-repair transesophageal real-time 3DE was performed in 35 patients undergoing undersized ring annuloplasty for IMR. An advanced modeling algorhythm was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with transthoracic echocardiography 6 months after repair.

Results

Annuloplasty significantly reduced septolateral diameter, commissural width, annular area, and tethering volume and significantly increased all segmental tethering angles (except A2). Intraoperative post-repair annular geometry and leaflet tethering did not differ significantly between patients with recurrent IMR (n = 9) and patients with non-recurrent IMR (n = 26). No intraoperative post-repair predictors of IMR recurrence could be identified.

Conclusions

Undersized ring annuloplasty changes mitral geometry acutely, exacerbates leaflet tethering, and generally fixes IMR acutely, but it does not always fix the delicate underlying chronic problem of continued left ventricular dilatation and remodeling. This may explain why pre-repair 3D valve geometry (which reflects chronic left ventricular remodeling) is highly predictive of recurrent IMR, whereas immediate post-repair 3D valve geometry (which does not completely reflect chronic left ventricular remodeling anymore) is not.
All-trans retinoic acid attenuates the progression of Ang II-induced abdominal aortic aneurysms in ApoE−/−mice
Authors: Xiao Jie , Liu Jinping , Lio Iohang , Yang Chuanlei , Chen Xing , Zhang Hua , Wang Shuxia , Wei Zhanjie
Published: July 2020

Background

To determine whether all-trans retinoic acid (ATRA) can influence the development of Angiotensin II (Ang II) induced experimental abdominal aortic aneurysms (AAAs).

Methods

Apolipoprotein E knock-out (ApoE−/−) mice were randomly assigned to 4 groups. Mice in the AAA and ATRA groups underwent continuous subcutaneous Ang II infusion for 28 days to induce AAA, while the Sham and Control groups were infused with saline. Systolic blood pressure was measured by the tail-cuff technique. The Control and ATRA groups received ATRA treatment. Aortic tissue samples were obtained at 28 days after surgery and evaluated by aortic diameter measurement, Western blotting, immunohistochemistry, and hematoxylin-eosin (H&E) and Verhoeff-Van Gieson (EVG) staining.

Results

The abdominal aortic diameter was significantly reduced in the ATRA group compared with the AAA group (3 of 12 (25%) vs 9 of 12 (75%),P < 0.05), and the ATRA group exhibited reduced blood pressure on days 7, 14, and 28. Low expression of angiotensin II receptor type 1 (AT1), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) and EVG staining revealed a significant reduction in the disruption of elastic fibers in the abdominal aortic tissue of the ATRA group compared to the AAA group. Western blot analysis indicated that protein levels of retinoic acid receptor α (RARα), MMP2, MMP9, and AT1 were dramatically affected by ATRA treatment.

Conclusions

In conclusion, ATRA attenuates the progression of Ang II-induced AAAs, possibly by downregulating MMP2, MMP9, and AT-1 expression.
Protocol for a randomized controlled trial comparing wound COmplications in elective midline laparotomies after FAscia Closure using two different Techniques Of Running sutures: COFACTOR trial
Authors: El Charif Mohamad Hadi , Hassan Zeina , Hoballah Jamal , Khalife Mohamad , Sbaity Eman
Published: July 2020

Background

Wound complications following midline laparotomies are common and the main source of postoperative morbidity including superficial or deep wound infection, skin dehiscence, fascia dehiscence, and incisional hernia. Abdominal closure complications are strongly associated with suture technique and material, in addition to other factors related to the patient and type of surgery performed. The traditional technique is to place the fascia sutures 1 cm apart and at least 1 cm away from the fascia edge. A Swedish study described a new technique of placing the sutures 5 mm apart and 5 mm away from the fascia edge, resulting in lower rates of abdominal wound complications. This study has a number of limitations. There is a need for improved quality evidence to convince the surgical community to change the closure technique of abdominal wounds aiming to reduce morbidity, which is exemplified in incisional hernias and other various postop complications.

Methods

This is a 1:1 randomized, controlled, patient- and assessor-blinded, parallel design, superiority trial, with a primary endpoint of incisional hernia at 1 year. The study will be conducted at AUBMC over a 3-year period. Patients planned for a non-emergent midline laparotomy for general surgery or vascular procedure will be randomized to either fascia closure technique. In order to detect a drop of 12% in the incidence of incisional hernia, with 80% power and an alpha of 0.05, we will need to recruit 114 patients per arm. After adjusting for loss to follow-up, target recruitment is 274 subjects. We will compare both arms for the primary, secondary, and exploratory outcomes, using chi-square or t test as appropriate. Univariate and multivariate logistic regression will be done.

Discussion

This trial will assess postop complications following abdominal midline wound closures via two different suturing techniques. This trial will generate evidence-based conclusions that will allow surgeons to assess the role of a new abdominal closure technique in decreasing short- and long-term postoperative complications, for a commonly performed procedure.

Trial registration

ClinicalTrials.gov NCT03527433. Registered on 17 May 2018 before starting participant enrollment.
Ileal proteomic changes associated with IL-25-mediated resistance against intestinal trematode infections
Authors: Álvarez-Izquierdo María , Guillermo Esteban J. , Muñoz-Antoli Carla , Toledo Rafael
Published: July 2020

Background

Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, which has been extensively used to investigate the factors that determine the rejection of intestinal helminths. In this sense, several studies have shown that IL-25 is critical for the development of resistance against E. caproni in mice. In fact, treatment of mice with recombinant IL-25 generates resistance against primary E. caproni infection. However, the mechanisms by which IL-25 induces resistance remain unknown.

Methods

To study the mechanisms responsible for resistance elicited by IL-25, we analyzed the ileal proteomic changes induced by IL-25 in mice and their potential role in resistance. To this purpose, we compared the protein expression profiles in the ileum of four experimental groups of mice: naïve controls; E. caproni-infected mice; rIL-25-treated mice; and rIL-25-treated mice exposed to E. caproni metacercariae.

Results

Quantitative comparison by 2D-DIGE showed significant changes in a total of 41 spots. Of these, 40 validated protein spots were identified by mass spectrometry corresponding to 24 proteins.

Conclusions

Our results indicate that resistance to infection is associated with the maintenance of the intestinal epithelial homeostasis and the regulation of proliferation and cell death. These results provide new insights into the proteins involved in the regulation of tissue homeostasis after intestinal infection and its transcendence in resistance.
Ten-eleven translocation methyl-cytosine dioxygenase 2 deficiency exacerbates renal ischemia-reperfusion injury
Authors: Yan Huan , Tan Li , Liu Yuqi , Huang Ning , Cang Jing , Wang Hao
Published: July 2020

Background

Ten-eleven translocation (Tet) methyl-cytosine dioxygenases (including Tet1/2/3)-mediated 5mC oxidation and DNA demethylation play important roles in embryonic development and adult tissue homeostasis. The expression of Tet2 and Tet3 genes are relatively abundant in the adult murine kidneys while Tet1 gene is expressed at a low level. Although Tet3 has been shown to suppress kidney fibrosis, the role of Tet2 in kidney physiology as well as renal ischemia-reperfusion (IR) injury is still largely unknown.

Results

Tet2−/− mice displayed normal kidney morphology and renal function as WT mice while the expression of genes associated with tight junction and adherens junction was impaired. At 24 h post-renal IR, Tet2−/− mice showed higher SCr and BUN levels, more severe tubular damage, and elevated expression of Kim1 and Ngal genes in the kidney in comparison with WT mice. Moreover, the transcriptomic analysis revealed augmented inflammatory response in the kidneys of Tet2−/− mice.

Conclusions

Tet2 is dispensable for kidney development and function at baseline condition while protects against renal IR injury possibly through repressing inflammatory response. Our findings suggest that Tet2 may be a potential target for the intervention of IR-induced acute kidney injury (AKI).
Extremely elevated serum alkaline phosphatase level upon treatment with teriparatide: a case report
Authors: Javinani Ali , Aghaei Meybodi Hamid Reza , Kavosi Hoda
Published: July 2020

Background

Teriparatide is a homolog of human parathyroid hormone (1–34), which is approved for the treatment of postmenopausal and glucocorticoid-induced osteoporosis. Several minor and transient side effects have been reported for teriparatide. However, controversial findings showed an increased risk of more significant adverse effects, including osteosarcoma in humans, although this finding has been demonstrated primarily in murine models.

Case presentation

We present a case of a 22-year-old Persian man with a previous history of systemic lupus erythematosus and glucocorticoid-induced osteoporosis. He had a previous history of joint hypermobility, idiopathic kyphoscoliosis, mitral valve prolapse, and bilateral congenital inguinal hernia, which were probably compatible with an inherited connective tissue disease. He was treated with teriparatide for 7 months because of glucocorticoid-induced osteoporosis. He was referred with a complaint of generalized bone pain and an extremely elevated serum alkaline phosphatase concentration of 6480 U/L (normal range, 80–306). A whole-body bone scan revealed a diffuse increased osseous uptake. Furthermore, the patient’s systemic lupus erythematosus was clinically inactive on the basis of laboratory findings during this period. The medication was discontinued, and the patient’s serum alkaline phosphatase level began to decline.

Conclusions

To the best of our knowledge, this is the first case of an osteoblast hyperactivation state observed during treatment with teriparatide. It appears that the osteoblastogenic effect of teriparatide might induce this condition and, most likely, osteosarcoma in certain populations. However, the potential influence of the patient’s young age, systemic lupus erythematosus, underlying inherited connective tissue disease, and medication use cannot be ignored. The potential risk factors of this side effect shall be studied in specific subpopulations of patients with osteoporosis in future studies.
Recent infection by Wolbachia alters microbial communities in wild Laodelphax striatellus populations
Authors: Duan Xing-Zhi , Sun Jing-Tao , Wang Lin-Ting , Shu Xiao-Han , Guo Yan , Keiichiro Matsukura , Zhu Yu-Xi , Bing Xiao-Li , Hoffmann Ary A. , Hong Xiao-Yue
Published: July 2020

Background

Host-associated microbial communities play an important role in the fitness of insect hosts. However, the factors shaping microbial communities in wild populations, including genetic background, ecological factors, and interactions among microbial species, remain largely unknown.

Results

Here, we surveyed microbial communities of the small brown planthopper (SBPH,Laodelphax striatellus) across 17 geographical populations in China and Japan by using 16S rRNA amplicon sequencing. Using structural equation models (SEM) and Mantel analyses, we show that variation in microbial community structure is likely associated with longitude, annual mean precipitation (Bio12), and mitochondrial DNA variation. However, aWolbachiainfection, which is spreading to northern populations of SBPH, seems to have a relatively greater role than abiotic factors in shaping microbial community structure, leading to sharp decreases in bacterial taxon diversity and abundance in host-associated microbial communities. Comparative RNA-Seq analyses betweenWolbachia-infected and -uninfected strains indicate that theWolbachiado not seem to alter the immune reaction of SBPH, althoughWolbachiaaffected expression of metabolism genes.

Conclusion

Together, our results identify potential factors and interactions among different microbial species in the microbial communities of SBPH, which can have effects on insect physiology, ecology, and evolution.
Development of a nomogram to predict 30-day mortality of patients with sepsis-associated encephalopathy: a retrospective cohort study
Authors: Yang Yang , Liang Shengru , Geng Jie , Wang Qiuhe , Wang Pan , Cao Yuan , Li Rong , Gao Guodong , Li Lihong
Published: July 2020

Background

Sepsis-associated encephalopathy (SAE) is related to increased short-term mortality in patients with sepsis. We aim to establish a user-friendly nomogram for individual prediction of 30-day risk of mortality in patients with SAE.

Methods

Data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC III) open source clinical database. SAE was defined by Glasgow Coma Score (GCS) < 15 or delirium at the presence of sepsis. Prediction model with a nomogram was constructed in the training set by logistic regression analysis and then undergone internal validation and sensitivity analysis.

Results

SAE accounted for about 50% in patients with sepsis and was independently associated with the 30-day mortality of sepsis. Variables eligible for the nomogram included patient’s age and clinical parameters on the first day of ICU admission including the GCS score, lactate, bilirubin, red blood cell distribution width (RDW), mean value of respiratory rate and temperature, and the use of vasopressor. Compared with Sequential Organ Failure Assessment (SOFA) and Logistic Organ Dysfunction System (LODS), the nomogram exhibited better discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.763 (95%CI 0.736–0.791, p < 0.001) and 0.753 (95%CI 0.713–0.794, p < 0.001) in the training and validation sets, respectively. The calibration plot revealed an adequate fit of the nomogram for predicting the risk of 30-day mortality in both sets. Regarding to clinical usefulness, the DCA of the nomogram exhibited greater net benefit than SOFA and LODS in both of the training and validation sets. Besides, the nomogram exhibited acceptable discrimination, calibration, and clinical usefulness in sensitivity analysis.

Conclusions

SAE is related to increased 30-day mortality of patients with sepsis. The nomogram presents excellent performance in predicting 30-day risk of mortality in SAE patients, which can be used to evaluate the prognosis of patients with SAE and may be more beneficial once specific treatments towards SAE are developed.
Processing of volcano infrasound using film sound audio post-production techniques to improve signal detection via array processing
Authors: Williams Ross Adrian , Perttu Anna , Taisne Benoit
Published: July 2020

The use of infrasound for the early detection of volcanic events has been shown to be effective over large distances, and unlike visual methods, is not weather dependent. Signals recorded via an infrasound array often have a poor signal to noise ratio, as other sources of infrasound are detected and recorded along with the volcano infrasound. Array processing software does not always detect known volcanic events, in part because of the amount of noise in the infrasound signal (Taisne et al., in: Pichon, Blanc, Hauchecorne (eds) Infrasound monitoring for atmospheric studies: challenges in middle atmosphere dynamics and societal benefits. Springer International Publishing, Cham, 2019). Resampling the infrasound into the audible range and then applying the acoustic noise reduction techniques of spectral subtraction prior to array processing is shown to improve signal detection of volcanic events. The discussed technique is applicable to any infrasound signal such as infrasound from anthropogenic sources like nuclear testing.
A simplification of rigorous atmospheric raytracing based on judicious rectilinear paths for near-surface GNSS reflectometry
Authors: Nikolaidou Thalia , Santos Marcelo , Williams Simon D. P. , Geremia-Nievinski Felipe
Published: July 2020

Atmospheric delays are known to cause biases in Global Navigation Satellite System Reflectometry (GNSS-R) altimetry applications, such as for sea-level monitoring. The main quantity of interest is the reflection-minus-direct or interferometric atmospheric delay. Recently, we have presented a rigorous raytracing procedure to account for linear and angular refraction in conjunction with reflection as observed from near-surface platforms. Here, we demonstrate the feasibility of simplifying the ray trajectory by imposing a rectilinear wave propagation model. Two variants were assessed, based on the apparent or refracted satellite direction on the one hand and the geometric or vacuum conditions on the other hand. The former was shown to agree with rigorous results in terms of interferometric radio length while the latter agreed in terms of the interferometric vacuum distance. Upon a judicious combination of the best aspects of the two rectilinear cases, we have defined a mixed variant with excellent agreement with rigorous raytracing in terms of interferometric atmospheric delay. We further showed that mapping functions developed for GNSS positioning cannot be reused for GNSS-R purposes without adaptations. Otherwise, the total atmospheric delay may be underestimated by up to 50% at low elevation angles. The present work facilitates the adaptation of existing atmospheric raytracing software for GNSS-R purposes.
Playing well with others: a case study of collective impact in the early care and education policy arena
Authors: Zuckerman Sarah J. , Garrett Amanda L. , Sarver Susan , Huddleston-Casas Catherine
Published: July 2020

The quality and quantity of early childhood care and education services have risen as a key reform area for influencing educational and economic outcomes. However, changes in this policy arena are stymied by the fragmentation of this policy arena. Collaborative approaches have been proposed to create systems-level change. Collective impact is one such approach; however, few examples exist in the early childhood care and education literature, especially at the state level. This ethnographic case study conceptualizes collective impact as a policy network capable of change in a fractured policy arena and reports the results from the first year of a statewide collective impact effort examines stakeholder perceptions of mobilization and development of a common agenda, or shared understandings. The results illustrate the importance of relationship building, ongoing attention to common understandings through multiple processes and mechanisms, the importance of the backbone organization, and the need to attend to mindset shifts that accompany early collective impact work.
Impact of systemic steroid treatment on talc pleurodesis: a report of six cases
Authors: Ishii Soichiro , Sakurashita Hiroshi , Mashida Emiko , Saeki Yasuyuki , Matsuo Hiroaki
Published: July 2020

Background

Instillation of sterile graded talc in the pleural space is performed to prevent reaccumulation of malignant pleural effusion after drainage. Talc is thought to encourage pleural adhesions as part of the repair process by provoking inflammation, suggesting that adhesions are less likely to form in patients taking corticosteroids or other drugs with anti-inflammatory effects. However, the relationship between steroid therapy and pleurodesis efficacy remains unclear.

Case presentation

We report the outcomes of six patients who underwent pleurodesis at Hiroshima University Hospital while being treated with systemic steroid therapy for non-cancer-related illnesses. Talc pleurodesis was successful at the first attempt in five of the six patients. The five successful cases were receiving low-dose oral prednisolone or methyl prednisolone (range, 1–20 mg/day) at the time of pleurodesis and had serum albumin levels ranging from 2.2 to 3.0 g/dL. In contrast, the patient in whom pleurodesis was unsuccessful was receiving a higher dose of prednisolone (40 mg/day) intravenously and had a relatively low serum album level (1.7 g/dL).

Conclusions

The outcome of pleurodesis may be affected by the dose and/or route of systemic steroid therapy. Further analysis with more patients will be necessary to clarify the relationship between steroid dosage and talc pleurodesis success rate.
An assessment of mutagenicity of chemical substances by (quantitative) structure–activity relationship
Authors: Honma Masamitsu
Published: July 2020

Currently, there are more than 100,000 industrial chemicals substances produced and present in our living environments. Some of them may have adverse effects on human health. Given the rapid expansion in the number of industrial chemicals, international organizations and regulatory authorities have expressed the need for effective screening tools to promptly and accurately identify chemical substances with potential adverse effects without conducting actual toxicological studies. (Quantitative) Structure–Activity Relationship ((Q)SAR) is a promising approach to predict the potential adverse effects of a chemical on the basis of its chemical structure. Significant effort has been devoted to the development of (Q) SAR models for predicting Ames mutagenicity, among other toxicological endpoints, owing to the significant amount of the necessary Ames test data that have already been accumulated. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M7 guideline for the assessment and control of mutagenic impurities in pharmaceuticals was established in 2014. It is the first international guideline that addresses the use of (Q) SAR instead of actual toxicological studies for human health assessment. Therefore, (Q) SAR for Ames mutagenicity now require higher predictive power for identifying mutagenic chemicals. This review introduces the advantages and features of (Q)SAR. Several (Q) SAR tools for predicting Ames mutagenicity and approaches to improve (Q) SAR models are also reviewed. Finally, I mention the future of (Q) SAR and other advanced in silico technology in genetic toxicology.
The impact of patient-reported outcome data from clinical trials: perspectives from international stakeholders
Authors: Cruz Rivera Samantha , McMullan Christel , Jones Laura , Kyte Derek , Slade Anita , Calvert Melanie
Published: July 2020

Background

Patient-reported outcomes (PROs) are increasingly collected in clinical trials as they provide unique information on the physical, functional and psychological impact of a treatment from the patient’s perspective. Recent research suggests that PRO trial data have the potential to inform shared decision-making, support pharmaceutical labelling claims and influence healthcare policy and practice. However, there remains limited evidence regarding the actual impact associated with PRO trial data and how to maximise PRO impact to benefit patients and society. Thus, our objective was to qualitatively explore international stakeholders’ perspectives surrounding:a)the impact of PRO trial data,b)impact measurement metrics, andc)barriers and facilitators to effectively maximise the impact of PRO trial data upon patients and society.

Methods

Semi-structured interviews with 24 international stakeholders were conducted between May and October 2018. Data were coded and analysed using reflexive thematic analysis.

Results

International stakeholders emphasised the impact of PRO trial data to benefit patients and society. Influence on policy-impact, including changes to clinical healthcare practice and guidelines, drug approval and promotional labelling claims were common types of PRO impact reported by interviewees. Interviewees suggested impact measurement metrics including: number of pharmaceutical labelling claims and interviews with healthcare practitioners to determine whether PRO data were incorporated in clinical decision-making. Key facilitators to PRO impact highlighted by stakeholders included: standardisation of PRO tools; consideration of health utilities when selecting PRO measures; adequate funding to support PRO research; improved reporting and dissemination of PRO trial data by key opinion leaders and patients; and development of legal enforcement of the collection of PRO data.

Conclusions

Determining the impact of PRO trial data is essential to better allocate funds, minimise research waste and to help maximise the impact of these data for patients and society. However, measuring the impact of PRO trial data through metrics is a challenging task, as current measures do not capture the total impact of PRO research. Broader international multi-stakeholder engagement and collaboration is needed to standardise PRO assessment and maximise the impact of PRO trial data to benefit patients and society.
First-year drug therapy of new-onset rheumatoid and undifferentiated arthritis: a nationwide register-based study
Authors: Muilu Paula , Rantalaiho Vappu , Kautiainen Hannu , Virta Lauri J. , Eriksson Johan G. , Puolakka Kari
Published: July 2020

Background

In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients.

Methods

From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed.

Results

A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone.

Conclusions

Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.
Optimization and immobilization of amylase produced by Aspergillus terreus using pomegranate peel waste
Authors: Ahmed Nehad E. , El Shamy Aliaa R. , Awad Hassan M.
Published: July 2020

Background

Amylases are amongst the most important hydrolytic enzymes that are used in numerous industrial uses reaching for food to pharmaceuticals. Immobilization of enzymes can proposal several assistances as reusability and retrieval from their products improve strength under both operating and storing environments.

Results

Marine fungal isolate was recovered from red sea water at Sharm El-Sheikh Province and was tested for amylase activity using different agricultural wastes as substrate. It was found that pomegranate peel was the best substrate for amylase production (339 U/ml). Thus, it was subjected for identifying by 18S rDNA gene. The phylogenetic analysis results indicated that this fungal isolate belonged toAspergillusspecies with similarity of 99% and named asAspergillus terrusSS_RS-NE. Its nucleotide sequences were deposited in NCBI GenBank under accession no. of MN901491. Some parameters affecting amylase activity using pomegranate peel as substrate were studied. The results denoted that, the highest amylase activity of 340.69 U/ml using 1.5% pomegranate peel at 30 °C, pH 6.0 on 5 days incubation time byAspergillus terreus. The produced crude enzyme was partially purified with 80% ammonium sulfate followed by dialysis. The enzyme activity was 1246 U/ml and 2411 U/ml employing ammonium sulfate precipitation and dialysis respectively.

The partially purified amylase was immobilized with 2% sodium alginate and the results showed the highest immobilized enzyme yield was 92.8%. The characterizations of immobilized amylase were studied and the results indicated that, the maximal immobilized amylase activity was 2522.5 U/ml with 2% starch as a substrate at optimum pH value of 6.5, temperature at 60 °C and 10 min reaction time in comparison to maximal free amylase enzyme at pH 5, 50 °C after 40 min. The results also indicated the immobilized amylase was stable at 60 °C for 20 min.

Conclusions

Aspergillus terrusSS_RS-NE (MN901491) was isolated and genetically identified. It has the ability to produce amylase enzyme using pomegranate peel waste with a yield of 339 U/ml. The crude enzyme was partially purified by ammonium sulfate followed by dialysis. The maximal immobilized amylase activity of 2522.5 U/ml was obtained under optimized some culture conditions and medium nutrient parameters.
Position and dimensions of the mental foramen and presence of the anterior loop in the Egyptian population: a retrospective CBCT study
Authors: Shalash M. , Khallaf Maram E. , Ali A. R.
Published: July 2020

Aim

Understanding the mental foramen (MF) position and prevalence and location of the anterior loop (AL) is important during clinical and surgical procedures close to the mental foramen to avoid damage to the neurovascular bundle. The current study was done to determine the location of the MF, its distance from the inferior border of the mandible, and prevalence of AL in Egyptian population using cone beam computed tomography (CBCT).

Methods

A retrospective analysis of CBCT images was done in this study. Images of Egyptian patients who have already been subjected to CBCT examination as part of their dental diagnosis and/or treatment planning were included according to the proposed eligibility criteria.

Results

This study showed that the most common location of the MF (43.8% on the left side and 67.9% on the right side) is located below the apex of the second premolar. The mean size of mental foramen showed a height of 3.32 mm in females, 3.60 mm in males, and a width of 3.41 mm in females and 3.59 mm in males. The mean value of distance from inferior border was 10.08 mm in females and 10.55 mm in males. Fifty-five percent of the cases showed presence of anterior loop.

Conclusion

These results are consistent with similar radiographic studies regarding size and location of MF and distances between MF and adjacent anatomic structures. The most common position of the MF is below the 2nd premolar. AL was found in more than half of the cases examined.
On the detectability of density change in steam-assisted gravity drainage reservoirs using muon tomography
Authors: Pieczonka Sara , Schouten Doug , Dabboor Oday , Osler Duncan , Braun Alexander
Published: July 2020

Muon tomography is applied to realistic density models of a steam-assisted gravity drainage (SAGD) reservoir at 1.25 and 5 years after initial reservoir production. Forward models of muon count and opacity based on the density models are computed, as well as inverse models of the synthetic muon observations for various simulated detector arrays. The results demonstrate that both phases of reservoir development, namely the rising phase and the spreading phase, can be resolved by muon detectors placed 30 m below the bitumen reservoir at 230 m total vertical depth. The total mass change in the reservoir was recovered from the inversion model and differs from the true mass change by 20%–29%. The spatial distribution of density change shows very good agreement in the horizontal direction, while the vertical is less well constrained in this modeled sensor array configuration. The inverse models provide improved insights into reservoir depletion patterns and indicate muon tomography to be an applicable tool for continuous reservoir monitoring. The numerical modeling approach developed herein is able to model a wide range of SAGD reservoir geometries and detector arrays toward planning of optimized monitoring solutions.
Reviews
Authors: Walker Kristoffer , Avakian Robert , Taylor Patrick
Published: July 2020

Numerical Methods of Exploration Seismology: With Algorithms in MATLAB, by Gary F. Margrave and Michael P. Lamoureux, ISBN 978-1-107-17014-8, 2019, Cambridge University Press, 450 p., US$79.99 (print), US$64 (eBook). Plate Tectonics and Great Earthquakes: 50 Years of Earth-shaking Events, by Lynn R. Sykes, ISBN 978-0-231-18688-9, 2019, Colombia University Press, 272 p., US$35 (print), US$35 (eBook). Geologic Structures of the Arctic Basin, by Alexey Piskarev, Victor Poselov, and Valery Kaminsky, ISBN 978-3-319-77741-2, 2019, Springer, 376 p., US$139.99 (print), US$109 (eBook).
Seismic Soundoff
Authors: Geary Andrew
Published: July 2020

How can couples best navigate dual careers? How do you balance work and life throughout a career? How can dual-career couples benefit companies? Eve Sprunt, author of A Guide for Dual-Career Couples, answers these questions and shows how management and individuals alike can activate the power of dual-career couples. The following is an excerpt from episode 81 of SEG's podcast, Seismic Soundoff. Listen to the full episode at https://seg.org/podcast/post/9041 .
Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index
Authors: Desmedt Christine , Fornili Marco , Clatot Florian , Demicheli Romano , De Bortoli Davide , Di Leo Angelo , Viale Giuseppe , de Azambuja Evandro , Crown John , Francis Prudence A. , Sotiriou Christos , Piccart Martine , Biganzoli Elia
Published: July 2020

PURPOSE

Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel–based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI).

PATIENTS AND METHODS

We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655 ; N = 2,887) comparing non-docetaxel– to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status.

RESULTS

There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04).

CONCLUSION

This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.
Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial
Authors: Sim Ie-Wen , Borromeo Gelsomina L. , Tsao Claudine , Hardiman Rita , Hofman Michael S. , Papatziamos Hjelle Christian , Siddique Musib , Cook Gary J. R. , Seymour John F. , Ebeling Peter R.
Published: July 2020

PURPOSE

Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option.

PATIENTS AND METHODS

In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life.

RESULTS

Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity.

CONCLUSION

Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.
Unwitting Accomplices: Endocrine Disruptors Confounding Clinical Care
Authors: Genco Matthew , Anderson-Shaw Lisa , Sargis Robert M
Published: July 2020

Burgeoning evidence over the last 25 years has identified myriad synthetic chemicals with the capacity to alter various aspects of hormone synthesis and action. These endocrine-disrupting chemicals (EDCs) have been linked to various diseases, including reproductive disorders, metabolic diseases, and developmental abnormalities, among others. Exposure to EDCs arises from industrial activity, use of personal and home care products, and consumption of contaminated food and water; however, the role of healthcare in exposing individuals to EDCs is grossly underappreciated. Indeed, through the use of medications as well as medical equipment and devices, healthcare providers are unknowing mediators of exposure to EDCs, chemicals that might not only promote disease but that may also antagonize the efficacy of treatments. The ethical implications of provider-dependent exposure are profound. A failure to disclose the endocrine-disrupting properties of medical interventions violates core principles of nonmaleficence, patient autonomy, and justice as well as the practice of informed consent. Furthermore, physicians’ lack of knowledge regarding EDCs in medical practice artificially skews risk–benefit calculations that are fundamental to informed medical decision-making. To combat this underappreciated ethical challenge, urgent action is required. Healthcare providers must be educated about endocrine disruption. Known EDCs, defined by endocrinologists, should be clearly labeled on all medical products, and all medication components and devices should be screened for endocrine-disrupting properties. Finally, communication strategies must be devised to empower patients with knowledge about these risks. Providing ethically competent care requires an open acknowledgment of endocrine risks imposed by the medical community that have heretofore been ignored.
Osteosarcopenia in Reproductive-Aged Women with Polycystic Ovary Syndrome: A Multicenter Case-Control Study
Authors: Kazemi Maryam , Jarrett Brittany Y , Parry Stephen A , Thalacker-Mercer Anna E , Hoeger Kathleen M , Spandorfer Steven D , Lujan Marla E
Published: July 2020

Context

Osteosarcopenia (loss of skeletal muscle and bone mass and/or function usually associated with aging) shares pathophysiological mechanisms with polycystic ovary syndrome (PCOS). However, the relationship between osteosarcopenia and PCOS remains unclear.

Objective

We evaluated skeletal muscle index% (SMI% = [appendicular muscle mass/weight (kg)] × 100) and bone mineral density (BMD) in PCOS (hyperandrogenism + oligoamenorrhea), and contrasted these musculoskeletal markers against 3 reproductive phenotypes (i): HA (hyperandrogenism + eumenorrhea) (ii); OA (normoandrogenic + oligoamenorrhea) and (iii), controls (normoandrogenic + eumenorrhea). Endocrine predictors of SMI% and BMD were evaluated across the groups.

Design, Setting, and Participants

Multicenter case-control study of 203 women (18-48 years old) in New York State.

Results

PCOS group exhibited reduced SMI% (mean [95% confidence interval (CI)]; 26.2% [25.1,27.3] vs 28.8% [27.7,29.8]), lower-extremity SMI% (57.6% [56.7,60.0] vs 62.5% [60.3,64.6]), and BMD (1.11 [1.08,1.14] vs 1.17 [1.14,1.20] g/cm2) compared to controls. PCOS group also had decreased upper (0.72 [0.70,0.74] vs 0.77 [0.75,0.79] g/cm2) and lower (1.13 [1.10,1.16] vs 1.19 [1.16,1.22] g/cm2) limb BMD compared to HA. Matsuda index was lower in PCOS vs controls and positively associated with SMI% in all groups (all Ps ≤ 0.05). Only controls showed associations between insulin-like growth factor (IGF) 1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (all Ps < 0.01). Unlike in PCOS, IGF-binding protein 2 was associated with SMI% in controls (r = 0.45) and HA (r = 0.67), and with upper limb BMD (r = 0.98) in HA (all Ps < 0.05).

Conclusions

Women with PCOS exhibit early signs of osteosarcopenia when compared to controls likely attributed to disrupted insulin function. Understanding the degree of musculoskeletal deterioration in PCOS is critical for implementing targeted interventions that prevent and delay osteosarcopenia in this clinical population.
The Vicious Circle of Left Ventricular Dysfunction and Diabetes: From Pathophysiology to Emerging Treatments
Authors: Cavallari Ilaria , Maddaloni Ernesto , Pieralice Silvia , Mulè Maria Tea , Buzzetti Raffaella , Ussia Gian Paolo , Pozzilli Paolo , Grigioni Francesco
Published: July 2020

Context

Diabetes and heart failure (HF) are 2 deadly and strictly related epidemic disorders. The aim of this review is to present an updated discussion of the epidemiology, pathophysiology, clinical presentation and treatment options for HF in diabetes.

Evidence Acquisition

Relevant references published up to February 2020 were identified through searches in PubMed. Quality was graded using the Newcastle-Ottawa score in observational studies and the Cochrane Collaboration tool in randomized studies.

Evidence Synthesis

Metabolic and neurohumoral derangements, oxidative stress, inflammation, micro- and macroangiopathy all contribute through complex molecular and cellular mechanisms to cardiac dysfunction in diabetes, which in turn, results as one the most frequent underlying conditions affecting up to 42% of patients with HF and causing a 34% increased risk of cardiovascular death. On top of traditional guideline-based HF medical and device therapies, equally effective in patients with and without diabetes, a new class of glucose-lowering agents acting through the sodium-glucose cotransporter 2 (SGLT2) inhibition showed impressive results in reducing HF outcomes in individuals with diabetes and represents an active area of investigation.

Conclusions

Diabetes and HF are strictly linked in a bidirectional and deadly vicious circle difficult to break. Therefore, preventive strategies and a timely diagnosis are crucial to improve outcomes in such patients. SGLT2 inhibitors represent a major breakthrough with remarkably consistent findings. However, it is still not clear whether their benefits may be definitely extended to patients with HF with preserved ejection fraction, to those without diabetes and in the acute setting.