bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between muscle strength, upper extremity fatigue resistance, work ability and upper extremity dysfunction in a sample of workers at a tertiary hospital
Authors: Fifolato Thaís Marques , Nardim Heloísa Correa Bueno , do Carmo Lopes Ester Rodrigues , Suzuki Karen A. Kawano , da Silva Natalia Claro , de Souza Serenza Felipe , Fonseca Marisa C. Registro
Published: June 2021

Background

Upper extremity musculoskeletal disorders negatively affect ability to perform activities of daily living, self-care and work. Therefore, outcome measurements that address muscle strength, fatigue resistance, functionality and work physical capacity must be defined to assess and plan specific actions to minimize them.

Objective

To investigate the association of upper extremity muscle strength with upper extremity fatigue resistance, work ability and upper extremity dysfunction in a sample of workers from a tertiary hospital.

Methods

Shoulder and elbow isokinetic strength were assessed by Biodex System 4™, isometric hand grip by JAMAR™, upper extremity fatigue resistance by Functional Impairment Test Hand and Neck/Shoulder/Arm (FIT-HaNSA), ability to work by the Work Ability Index and upper extremity dysfunction by the Quick-Disabilities of the Arm, Shoulder and Hand QuickDASH-Br questionnaire. The Nordic questionnaire and Numeric Pain Rating Scale (NPRS) were used for pain description. The associations were analysed by Spearman’s correlation coefficient (rho) (p < 0.05).

Results

Twenty-seven participants: 59.2% women; mean age 46 years old; 70.3% obese/overweight; 62.9% active with predominantly dynamic muscle contraction work. Besides predominance of good to moderate work ability (81.4%) and comorbidities (37%), all participants had symptoms of the upper extremities for at least 12 months, with a predominance of low-intensity in the shoulder (55.5%). In addition, 88.8% reported pain in other segments. Muscle strength of abduction (rho = 0.49), adduction (rho = 0.40), internal rotation (rho = 0.44) and hand grip (rho = 0.68) presented moderate correlation with FIT-HaNSA. Hand grip (rho = − 0.52) showed moderate correlation with upper extremity dysfunction.

Conclusions

The results of this preliminary study suggested the association of shoulder strength with fatigue resistance. Also, hand grip strength was associated with upper extremity dysfunction and fatigue resistance. No association was found with the Work Ability Index in this sample. So, it is suggested that hand grip and shoulder strength could be outcome measurements used for future interventions focused on upper extremity preventive exercises to improve strength and fatigue resistance of workers at risk for the development of musculoskeletal disorders. Other individual, psychosocial and organizational risk factors must also be considered as influences on upper extremity function.
Exploring the relationship between spiritual well-being and death anxiety in patients with gynecological cancer: a cross-section study
Authors: Feng Yue , Liu Xingcan , Lin Tangwei , Luo Biru , Mou Qianqian , Ren Jianhua , Chen Jing
Published: June 2021

Background

In recent years, spiritual well-being has gradually gained the attention of health care providers in China, especially those in oncology departments, who have recognized the importance of improving spiritual well-being in cancer patients. Since most of the current research on spiritual well-being has been carried out in areas with religious beliefs, this study was conducted in the context of no development of formal religion. The purpose of this study was to explore the relationship between death anxiety and spiritual well-being and the related factors of spiritual well-being among gynecological cancer patients.

Methods

This cross-section study was conducted among 586 gynecological cancer patients. The European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-spiritual well-being32 (EORTC QLQ-SWB32) and Templer's Death Anxiety Scale (T-DAS) were used to measure spiritual well-being and death anxiety. The Multiple Linear Regression Model was used to determine the relationship between spiritual well-being and death anxiety.

Results

For all participants, the highest QLQ-SWB32 centesimal score was 75.13 on the Relationship with Other scale, and the lowest was 60.33 on the Relationship with Someone or Something Greater Scale. The mean Death Anxiety score was 5.31 (SD 3.18). We found that Relationship with Someone or Something Greater was the only scale not associated with death anxiety. Overall, patients with lower death anxiety have a higher level of spiritual well-being. Besides, a high Relationship with Other score was associated with living with a partner (B = 2.471, P < 0.001) and married (B = -6.475, P = 0.001). Patients with higher Global-SWB were retired (B = 0.387, P = 0.019).

Conclusions

Our study found that the spiritual well-being of patients with gynecological cancer in China was no worse than in other countries with religious beliefs and patients with lower death anxiety have a higher level of spiritual well-being. Clinical staff should pay attention to the spiritual health of cancer patients, and spiritual care should be regarded as an essential element in cancer care.
Correction to: Necessity for subsequent surgery in women of child-bearing age with positive margins after conization
Authors: Wang Xinmei , Xu Juan , Gao Yang , Qu Pengpeng
Published: June 2021

Following the publication of the original article [1], we were notified that Pengpeng Qu should be marked as corresponding author.
Ethical factors determining ECMO allocation during the COVID-19 pandemic
Authors: Dao Bernadine , Savulescu Julian , Suen Jacky Y. , Fraser John F. , Wilkinson Dominic J. C.
Published: June 2021

Background

ECMO is a particularly scarce resource during the COVID-19 pandemic. Its allocation involves ethical considerations that may be different to usual times. There is limited pre-pandemic literature on the ethical factors that ECMO physicians consider during ECMO allocation. During the pandemic, there has been relatively little professional guidance specifically relating to ethics and ECMO allocation; although there has been active ethical debate about allocation of other critical care resources. We report the results of a small international exploratory survey of ECMO clinicians’ views on different patient factors in ECMO decision-making prior to and during the COVID-19 pandemic. We then outline current ethical decision procedures and recommendations for rationing life-sustaining treatment during the COVID-19 pandemic, and examine the extent to which current guidelines for ECMO allocation (and reported practice) adhere to these ethical guidelines and recommendations.

Methods

An online survey was performed with responses recorded between mid May and mid August 2020. Participants (n = 48) were sourced from the ECMOCard study group—an international group of experts (n = 120) taking part in a prospective international study of ECMO and intensive care for patients during the COVID-19 pandemic. The survey compared the extent to which certain ethical factors involved in ECMO resource allocation were considered prior to and during the pandemic.

Results

When initiating ECMO during the pandemic, compared to usual times, participants reported giving more ethical weight to the benefit of ECMO to other patients not yet admitted as opposed to those already receiving ECMO, (p < 0.001). If a full unit were referred a good candidate for ECMO, participants were more likely during the pandemic to consider discontinuing ECMO from a current patient with low chance of survival (53% during pandemic vs. 33% priorp = 0.002). If the clinical team recommends that ECMO should cease, but family do not agree, the majority of participants indicated that they would continue treatment, both in usual circumstances (67%) and during the pandemic (56%).

Conclusions

We found differences during the COVID-19 pandemic in prioritisation of several ethical factors in the context of ECMO allocation. The ethical principles prioritised by survey participants were largely consistent with ECMO allocation guidelines, current ethical decision procedures and recommendations for allocation of life-sustaining treatment during the COVID-19 pandemic.
Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blind placebo controlled randomized clinical trial
Authors: Moludi Jalal , Kafil Hossein Samadi , Qaisar Shaimaa A. , Gholizadeh Pourya , Alizadeh Mohammad , Vayghyan Hamed Jafari
Published: June 2021

Purpose

Alterations in the gut microbiome (dysbiosis) has been associated with increased microbial translocation, leading to chronic inflammation in coronary artery disease (CAD). It has been proposed that modulation of gut microbiota by probiotic might modify metabolic endotoxemia. Therefore, the purpose of this study was to examine the effects of Lactobacillus rhamnosus GG (LGG) on endotoxin level, and biomarkers of inflammation in CAD participants.

Methods

This study was a 12-weeks randomized, double-blind, and intervention on 44 patients with CAD. Patients were randomly allocated to receive either one LGG capsule 1.6 × 109 colony-forming unit (CFU) or the placebo capsules for 12 weeks. In addition, all the participants were also prescribed a calorie-restricted diet. Serum levels of interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and lipopolysaccharide (LPS), were assessed before and after the intervention.

Results

A significant decrease in IL1-Beta concentration (− 1.88 ± 2.25, vs. 0.50 ± 1.58 mmol/L, P = 0.027), and LPS levels (− 5.88 ± 2.70 vs. 2.96+ 5.27 mg/L, P = 0.016), was observed after the probiotic supplementation compared with the placebo. Participants who had ≥2.5 kg weight loss showed significantly improved cardiovascular-related factors, compared to patients with < 2.5 kg weight reduction, regardless of the supplement they took.

Conclusion

These data provide preliminary evidence that probiotic supplementation has beneficial effects on metabolic endotoxemia, and mega inflammation in participants with CAD.
Development of a non-invasive method for skin cholesterol detection: pre-clinical assessment in atherosclerosis screening
Authors: Ni Jingshu , Hong Haiou , Zhang Yang , Tang Shiqi , Han Yongsheng , Fang Zhaohui , Zhang Yuanzhi , Zhou Nan , Wang Quanfu , Liu Yong , Li Zhongsheng , Wang YiKun , Dong Meili
Published: June 2021

Background

Establishing a high-accuracy and non-invasive method is essential for evaluating cardiovascular disease. Skin cholesterol is a novel marker for assessing the risk of atherosclerosis and can be used as an independent risk factor of early assessment of atherosclerotic risk.

Methods

We propose a non-invasive skin cholesterol detection method based on absorption spectroscopy. Detection reagents specifically bind to skin cholesterol and react with indicator to produce colored products, the skin cholesterol content can be obtained through absorption spectrum information on colored products detected by non-invasive technology. Gas chromatography is used to measure cholesterol extracted from the skin to verify the accuracy and reliability of the non-invasive test method. A total of 342 subjects were divided into normal group (n = 115), disease group (n = 110) and risk group (n = 117). All subjects underwent non-invasive skin cholesterol test. The diagnostic accuracy of the measured value was analyzed by receiver-operating characteristic (ROC) curve.

Results

The proposed method is able to identify porcine skin containing gradient concentration of cholesterol. The values measured by non-invasive detection method were significantly correlated with gas chromatography measured results (r = 0.9074, n = 73, p < 0.001). Bland–Altman bias was − 72.78 ± 20.03 with 95% limits of agreement − 112.05 to − 33.51, falling within the prespecified clinically non-significant range. We further evaluated the method of patients with atherosclerosis and risk population as well as normal group, patients and risk atherosclerosis group exhibited higher skin cholesterol content than normal group (all P < 0.001). The area under the ROC curve for distinguishing Normal/Disease group was 0.8642 (95% confidence interval, 0.8138 to 0.9146), meanwhile, the area under the ROC curve for distinguishing Normal/Risk group was 0.8534 (95% confidence interval, 0.8034 to 0.9034).

Conclusions

The method demonstrated its capability of detecting different concentration of skin cholesterol. This non-invasive skin cholesterol detection system may potentially be used as a risk assessment tool for atherosclerosis screening, especially for a large population.
Correction to: Comparative analysis of ankyrin (ANK) genes of five capripoxviruses isolate strains from Xinjiang province in China
Authors: He Chuanchuan , Tong Jianjun , Zhang Xueping , Tuohetiniyazi Milikaimu , Zhang Yu , Li Youwen
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
COVID-19 ARDS is characterized by higher extravascular lung water than non-COVID-19 ARDS: the PiCCOVID study
Authors: Shi Rui , Lai Christopher , Teboul Jean-Louis , Dres Martin , Moretto Francesca , De Vita Nello , Pham Tài , Bonny Vincent , Mayaux Julien , Vaschetto Rosanna , Beurton Alexandra , Monnet Xavier
Published: June 2021

Background

In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin.

Methods

Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020.

Results

Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14–21) vs. 15 (11–19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18–27) vs. 21 (15–24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70–109) vs. 100 (80–124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort.

Conclusion

Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups.

Trial registration number and date of registration

ClinicalTrials.gov (NCT04337983). Registered 30 March 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983.
Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation
Authors: Padmanabhan Nisha , Kyon Huang Kie , Boot Arnoud , Lim Kevin , Srivastava Supriya , Chen Shuwen , Wu Zhiyuan , Lee Hyung-Ok , Mukundan Vineeth T. , Chan Charlene , Chan Yarn Kit , Xuewen Ong , Pitt Jason J. , Isa Zul Fazreen Adam , Xing Manjie , Lee Ming Hui , Tan Angie Lay Keng , Ting Shamaine Ho Wei , Luftig Micah A. , Kappei Dennis , Kruger Warren D. , Bian Jinsong , Ho Ying Swan , Teh Ming , Rozen Steve George , Tan Patrick
Published: June 2021

Background

CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs.

Results

We identify the cystathionine beta-synthase enzyme (CBS) as a highly recurrent target of epigenetic silencing in CIMP GC. Likewise, we show that CBS epimutations are significantly associated with CIMP in various other cancers, occurring even in premalignant gastroesophageal conditions and longitudinally linked to clinical persistence. Of note, CRISPR deletion of CBS in normal gastric epithelial cells induces widespread DNA methylation changes that overlap with primary GC CIMP patterns. Reflecting its metabolic role as a gatekeeper interlinking the methionine and homocysteine cycles, CBS loss in vitro also causes reductions in the anti-inflammatory gasotransmitter hydrogen sulfide (H2S), with concomitant increase in NF-κB activity. In a murine genetic model of CBS deficiency, preliminary data indicate upregulated immune-mediated transcriptional signatures in the stomach.

Conclusions

Our results implicate CBS as a bi-faceted modifier of aberrant DNA methylation and inflammation in GC and highlights H2S donors as a potential new therapy for CBS-silenced lesions.
An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years
Authors: Campochiaro Corrado , Allanore Yannick
Published: June 2021

New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.
Subcellular localization of the mouse PRAMEL1 and PRAMEX1 reveals multifaceted roles in the nucleus and cytoplasm of germ cells during spermatogenesis
Authors: Liu Wan-Sheng , Lu Chen , Mistry Bhavesh V.
Published: June 2021

Background

Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen (CTA) that is predominantly expressed in normal gametogenic tissues and a variety of tumors. Members of the PRAME gene family encode leucine-rich repeat (LRR) proteins that provide a versatile structural framework for the formation of protein–protein interactions. As a nuclear receptor transcriptional regulator, PRAME has been extensively studied in cancer biology and is believed to play a role in cancer cell proliferation by suppressing retinoic acid (RA) signaling. The role of the PRAME gene family in germline development and spermatogenesis has been recently confirmed by a gene knockout approach. To further understand how PRAME proteins are involved in germ cell development at a subcellular level, we have conducted a systematic immunogold electron microscopy (IEM) analysis on testis sections of adult mice with gene-specific antibodies from two members of the mouse Prame gene family: Pramel1 and Pramex1. Pramel1 is autosomal, while Pramex1 is X-linked, both genes are exclusively expressed in the testis.

Results

Our IEM data revealed that both PRAMEL1 and PRAMEX1 proteins were localized in various cell organelles in different development stages of spermatogenic cells, including the nucleus, rER, Golgi, mitochondria, germ granules [intermitochondrial cement (IMC) and chromatoid body (CB)], centrioles, manchette, and flagellum. Unlike other germ cell-specific makers, such as DDX4, whose proteins are evenly distributed in the expressed-organelle(s), both PRAMEL1 and PRAMEX1 proteins tend to aggregate together to form clusters of protein complexes. These complexes were highly enriched in the nucleus and cytoplasm (especially in germ granules) of spermatocytes and spermatids. Furthermore, dynamic distribution of the PRAMEL1 protein complexes were observed in the microtubule-based organelles, such as acroplaxome, manchette, and flagellum, as well as in the nuclear envelope and nuclear pore. Dual staining with PRAMEL1 and KIF17B antibodies further revealed that the PRAMEL1 and KIF17B proteins were co-localized in germ granules.

Conclusion

Our IEM data suggest that the PRAMEL1 and PRAMEX1 proteins are not only involved in transcriptional regulation in the nucleus, but may also participate in nucleocytoplasmic transport, and in the formation and function of germ cell-specific organelles during spermatogenesis.
Joint contributions of the gut microbiota and host genetics to feed efficiency in chickens
Authors: Wen Chaoliang , Yan Wei , Mai Chunning , Duan Zhongyi , Zheng Jiangxia , Sun Congjiao , Yang Ning
Published: June 2021

Background

Feed contributes most to livestock production costs. Improving feed efficiency is crucial to increase profitability and sustainability for animal production. Host genetics and the gut microbiota can both influence the host phenotype. However, the association between the gut microbiota and host genetics and their joint contribution to feed efficiency in chickens is largely unclear.

Results

Here, we examined microbial data from the duodenum, jejunum, ileum, cecum, and feces in 206 chickens and their host genotypes and confirmed that the microbial phenotypes and co-occurrence networks exhibited dramatic spatial heterogeneity along the digestive tract. The correlations between host genetic kinship and gut microbial similarities within different sampling sites were weak, with coefficients ranging from − 0.07 to 0.08. However, microbial genome-wide analysis revealed that genetic markers near or inside the genes MTHFD1L and LARGE1 were associated with the abundances of cecal Megasphaera and Parabacteroides, respectively. The effect of host genetics on residual feed intake (RFI) was 39%. We further identified three independent genetic variations that were related to feed efficiency and had a modest effect on the gut microbiota. The contributions of the gut microbiota from the different parts of the intestinal tract on RFI were distinct. The cecal microbiota accounted for 28% of the RFI variance, a value higher than that explained by the duodenal, jejunal, ileal, and fecal microbiota. Additionally, six bacteria exhibited significant associations with RFI. Specifically, lower abundances of duodenal Akkermansia muciniphila and cecal Parabacteroides and higher abundances of cecal Lactobacillus, Corynebacterium, Coprobacillus, and Slackia were related to better feed efficiency.

Conclusions

Our findings solidified the notion that both host genetics and the gut microbiota, especially the cecal microbiota, can drive the variation in feed efficiency. Although host genetics has a limited effect on the entire microbial community, a small fraction of gut microorganisms tends to interact with host genes, jointly contributing to feed efficiency. Therefore, the gut microbiota and host genetic variations can be simultaneously targeted by favoring more-efficient taxa and selective breeding to improve feed efficiency in chickens.
Regional lithium prescription rates and recurrence in bipolar disorder
Authors: Sköld Martin , Rolstad Sindre , Joas Erik , Kardell Mathias , Pålsson Erik , Goodwin Guy M. , Landén Mikael
Published: June 2021

Background

Lithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.

Aims

To estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.

Method

Data from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately.

Results

Lithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately.

Conclusions

The advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.
Conventional risk prediction models fail to accurately predict mortality risk among patients with coronavirus disease 2019 in intensive care units: a difficult time to assess clinical severity and quality of care
Authors: Endo Hideki , Ohbe Hiroyuki , Kumasawa Junji , Uchino Shigehiko , Hashimoto Satoru , Aoki Yoshitaka , Asaga Takehiko , Hashiba Eiji , Hatakeyama Junji , Hayakawa Katsura , Ichihara Nao , Irie Hiromasa , Kawasaki Tatsuya , Kurosawa Hiroshi , Nakamura Tomoyuki , Okamoto Hiroshi , Shigemitsu Hidenobu , Takaki Shunsuke , Takimoto Kohei , Uchida Masatoshi , Uchimido Ryo , Miyata Hiroaki
Published: June 2021

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, it has remained unknown whether conventional risk prediction tools used in intensive care units are applicable to patients with COVID-19. Therefore, we assessed the performance of established risk prediction models using the Japanese Intensive Care database. Discrimination and calibration of the models were poor. Revised risk prediction models are needed to assess the clinical severity of COVID-19 patients and monitor healthcare quality in ICUs overwhelmed by patients with COVID-19.
Analysis of hard tissue facial symmetry after unilateral mandibular reconstruction
Authors: Khaghaninejad Mohamad Saleh , Khojastepour Leila , Ahmadi Hanie , Tavanafar Saeid , Ebrahimi Alireza , Mahjoori-Ghasrodashti Mohammad
Published: June 2021

Background

This study aimed to determine how successful reconstruction of the mandible can recover the symmetry.

Materials and methods

All patients who underwent surgical treatment for unilateral mandibular reconstruction in 4 years were retrospectively examined. Bilateral differences of gonion (GO) positions were measured in 3 dimensions based on immediate postoperative computed tomography. The data collected was analyzed in 3 ways: First, the comparison of bilateral differences of GO in 3 dimensions. Second, the mean Asymmetry Index in control subjects was used to divide all cases into three groups: “Symmetry,” “Asymmetry,” and “Marked asymmetry.” Third, “maximum normal asymmetry” was calculated, and all cases were categorized as below and above maximum normal asymmetry. The difference between two gonial angles was used to determine the amount of asymmetry.

Results

Forty-seven patients and 47 normal adults were enrolled. The mean bilateral GO difference in the control group was higher than in the study group patients, but it was not statistically significant. The mean Asymmetry Index for the control group was not also significantly higher than the study cases. The study group was “Symmetric” in 78.7% of the cases whereas the control group in 91.4%, 19.1% of the study group and 8.5% of controls were “Asymmetric,” and 2.1% of study cases and 0% of controls were “Markedly Asymmetric.” Maximum normal asymmetry was 82.9% in the study group and 97.8% in the control group. The mean differences between the right and left gonial angles were higher in the study group, but it was not significant (P= 0.1).

Conclusions

Our study’s results showed that bilateral symmetry in mandibular reconstruction patients was satisfactory and similar to the normal individuals.
Introduction to this special section: The role of advanced modeling in enhanced carbon storage
Authors: Paffenholz Josef
Published: June 2021

To limit the warming of the planet to no more than a 2°C increase, models show that net-zero release of anthropomorphic CO2 must be achieved by the middle of the century. For the foreseeable future, the majority of the world's energy will still be provided by fossil fuels, so other methods, besides expanding the contribution of renewable energy, are needed in order to achieve this goal. According to the Intergovernmental Panel on Climate Change (IPCC), carbon capture and sequestration (CCS) is one such method, without which the cost to achieve the 2°C target would more than double. To achieve this climate goal, CCS efforts must increase by approximately 100-fold from current levels within the next 20 years. Geophysical simulations on suitable geologic models will provide an important tool to streamline and accelerate the vast expansion of geophysical site characterization and long-term monitoring tasks required for industrial-scale CCS to succeed.
A three-component optical sensor for borehole seismic applications
Authors: Haldorsen Jakob B. U. , Christensen Caleb , Metzbower D. Rick , Berzanskis Audrius , Machnizh Jorge , Bergery Guillaume , Lesnikov Vladislav , Verliac Michel , Merry Harold , Dawood Ali A.
Published: June 2021

We describe a new optical three-component accelerometer for borehole applications. Field data acquired in early 2020 in a fiber-optic-instrumented well in Houston, Texas, show that the new optical accelerometer is a viable borehole seismic sensor, measuring signals at frequencies from subhertz to hundreds of hertz. It is argued that an array of these sensors could be used to complement distributed acoustic sensing (DAS) technology to compensate for the inability of DAS sensors to measure wavefield polarization. This hybrid fiber-optic receiver array would be a fully optical wide-bandwidth sensor array without any electronics in the well. With a maximum operational temperature expected to exceed 200°C, this array would not be affected significantly by possible high temperatures in the near-reservoir section of the well.
Acquisition/Processing
Authors: Woog Lionel J. , Vassiliou Anthony , Stromberg Rodney
Published: June 2021

In seismic data processing, static corrections for near-surface velocities are derived from first-break picking. The quality of the static corrections is paramount to developing an accurate shallow velocity model, a model that in turn greatly impacts the subsequent seismic processing steps. Because even small errors in first-break picking can greatly impact the seismic velocity model building, it is necessary to pick high-quality traveltimes. Whereas various artificial intelligence-based methods have been proposed to automate the process for data with medium to high signal-to-noise ratio (S/N), these methods are not applicable to low-S/N data, which still require intensive labor from skilled operators. We successfully replace 160 hours of skilled human work with 10 hours of processing by a single NVIDIA Quadro P6000 graphical processing unit by reducing the number of human picks from the usual 5%–10% to 0.19% of available gathers. High-quality inferred picks are generated by convolutional neural network-based machine learning trained from the human picks.
Memorial
Authors: Paterson Norman
Published: June 2021

• Roger Watson, 1936–2021
The Ethical Imperative of Equity in Oncology: Lessons Learned From 2020 and a Path Forward
Authors: Marron Jonathan M. , Charlot Marjory , Gaddy Jacquelyne , Rosenberg Abby R.
Published: June 2021

The COVID-19 pandemic and the simultaneous increased focus on structural racism and racial/ethnic disparities across the United States have shed light on glaring inequities in U.S. health care, both in oncology and more generally. In this article, we describe how, through the lens of fundamental ethical principles, an ethical imperative exists for the oncology community to overcome these inequities in cancer care, research, and the oncology workforce. We first explain why this is an ethical imperative, centering the discussion on lessons learned during 2020. We continue by describing ongoing equity-focused efforts by ASCO and other related professional medical organizations. We end with a call to action—all members of the oncology community have an ethical responsibility to take steps to address inequities in their clinical and academic work—and with guidance to practicing oncologists looking to optimize equity in their research and clinical practice.
Beyond the Androgen Receptor: The Sequence, the Mutants, and New Avengers in the Treatment of Castrate-Resistant Metastatic Prostate Cancer
Authors: Westaby Daniel , Viscuse Paul V. , Ravilla Rahul , de la Maza Maria de los Dolores Fenor , Hahn Andrew , Sharp Adam , de Bono Johann , Aparicio Ana , Fleming Mark T.
Published: June 2021

Targeting the androgen receptor by depriving testosterone with gonadotropin-releasing hormone agonists or antagonists, or surgical castration, has been the backbone of metastatic prostate cancer treatment. Although most prostate cancers initially respond to androgen deprivation, metastatic castration-resistant prostate cancer evolves into a heterogeneous disease with diverse drivers of progression and mechanisms of therapeutic resistance. Development of castrate resistance phenotype is associated with lethality despite the recent noteworthy strides gained via increase in therapeutic options. Identification of novel therapeutics to further improve survival and achieve durable responses in metastatic castration-resistant prostate cancer is a clinical necessity. In this review, we outline the existing avengers for treatment of metastatic castration-resistant prostate cancer by clinical presentation, placing into context the clinical state of the patient, such as burden of disease and symptoms. Doing so might aid in the ability to optimize the sequence of agents and allow for maximal exposure to life-prolonging therapeutics. Realizing the limitations of the androgen signaling inhibition, we explore the androgen-indifferent prostate cancer: the mutants. Classically, these subtypes have been associated with variant histology, but androgen-indifferent prostate cancer features are now frequently observed in association with heterogeneous morphologies, including double-negative prostate cancers, lacking both androgen receptor and neuroendocrine features, or clinicopathologic criteria, such as the aggressive variant prostate cancer criteria. The framework of new avengers against metastatic castration-resistant prostate cancer based on mechanism, including DNA repair, immune checkpoint inhibition, PTEN/PI3K/AKT pathway, prostate-specific membrane antigen targets, bispecific T-cell engagers, and radionuclide therapies, is summarized in this review.
Evaluation of intra-tumoral (IT) SD-101 and pembrolizumab (Pb) in combination with paclitaxel (P) followed by AC in high-risk HER2-negative (HER2-) stage II/III breast cancer: Results from the I-SPY 2 trial.
Authors: Chien Amy Jo , Soliman Hatem Hussein , Ewing Cheryl Ann , Boughey Judy Caroline , Campbell Michael J. , Rugo Hope S. , Wallace Anne M. , Albain Kathy S. , Stringer-Reasor Erica Michelle , Church An L , Kalinsky Kevin , Elias Anthony D. , Mitri Zahi Ibrahim , Clark Amy Sanders , Nanda Rita , Thomas Alexandra , Yau Christina ,   I-SPY 2 Consortium, Berry Donald A , Esserman Laura
Published: June 2021

508

Background: I-SPY 2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. SD-101 is an investigational Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide that stimulates the production of IFN-α and interleukin (IL)-12, functional maturation of plasmacytoid dendritic cells, and production of cytotoxic antibodies. IT SD-101 was combined with systemic anti-PD-1 antibody Pb to investigate the antitumor and immunologic activity of this novel immunotherapeutic strategy. Methods: Women with tumors ≥ 2.5cm were eligible for screening. Only pts (pts) with HER2- disease were eligible for this treatment. Treatment included weekly P x 12 in combination with IT SD-101 2 mg/ml (1 ml for T2 tumors, 2 ml for >T3 tumors) weekly x 4, then q3 weeks x 2, and IV Pb q3 weeks x 4, followed by doxorubicin/cyclophosphamide (AC) q2-3 weeks x 4 (SD-101+Pembro 4). Pts in the control arm received weekly P x 12 followed by AC q2-3 weeks x 4. The I-SPY 2 methods have been previously published. This investigational arm was eligible for graduation (>85% chance of success in a 300-person phase 3 neoadjuvant trial) in 3 of 10 pre-defined signatures: HER2-, hormone receptor (HR)+/HER2- and HR-/HER2-. Results: 75 pts were randomized and evaluable in SD-101+Pembro 4 treatment arm. The control arm included 329 historical controls enrolled since April 2010. The study arm was stopped due to maximal patient accrual. Pt characteristics were balanced; 56% HR+, 44% HR-. The probability that SD-101+Pembro4 was superior to control exceeded 97% for all eligible tumor signatures, but did not reach the threshold for graduation in any of the signatures. However, it is notable that the rate of pCR/Residual Cancer Burden 1 (RCB1) in the HR+/HER2- signature was 51%. Preliminary safety events for SD-101+Pembro 4 include increased rates of fever, neutropenia, febrile neutropenia, transaminitis, and immune-related events, including adrenal insufficiency. Conclusions: The SD-101+Pembro 4 regimen was active but did not meet the pre-specified threshold for graduation in I-SPY 2. pCR/RCB 1 analysis suggests improved response in the HR+/HER-negative signature compared to control. The clinical significance of these findings needs to be weighed against the potential risk of immune-related toxicities. Clinical trial information: NCT01042379. [Table: see text]
PCOS Features and Steroid Profiles Among Young Adult Women with a History of Premature Adrenarche
Authors: Tennilä Jussi , Jääskeläinen Jarmo , Utriainen Pauliina , Voutilainen Raimo , Häkkinen Merja , Auriola Seppo , Morin-Papunen Laure , Liimatta Jani
Published: June 2021

Context

Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS).

Objective

To study features of PCOS in young adult women with a history of PA.

Methods

Thirty PA and 42 control females were followed from prepuberty to young adulthood (median age 18.1 years). The main outcome measures were ovarian function, the use of contraceptives, and clinical and biochemical indicators of hyperandrogenism.

Results

We found no differences in the use of hormonal contraceptives (50 vs 50%, PA vs controls, respectively; P > .999), indication for using contraceptives (P = .193), or in the history of oligo- (17 vs 26%, P = .392) and amenorrhea (0 vs 0%, P > .999). Among women not using hormonal contraceptives, those with a history of PA had a higher prevalence of hirsutism (27 vs 0%, P = .023) but not acne (87 vs 67%, P = .252). Steroid profiles were broadly comparable between the groups, but PA women had lower sex hormone–binding globulin (SHBG) concentrations (30.1 vs 62.4 nmol/L, P < .001) resulting in higher free androgen index (3.94 vs 2.14, P < .001). The difference in SHBG levels persisted through body mass index adjustment. SHBG correlated negatively with the homeostasis model assessment for insulin resistance (r –0.498, P = .003). Anti-Müllerian hormone concentrations were comparable between the groups (39.3 vs 32.1 pmol/L, P = .619).

Conclusion

PA was not associated with evident ovarian dysfunction in young adult women. However, women with a history of PA had decreased SHBG levels and thus, increased bioavailability of circulating androgens.
Tall cell percentage alone in PTC without aggressive features should not guide patients’ clinical management
Authors: Poma Anello Marcello , Viola David , Macerola Elisabetta , Proietti Agnese , Molinaro Eleonora , De Vietro Dario , Elisei Rossella , Materazzi Gabriele , Miccoli Paolo , Basolo Fulvio , Ugolini Clara
Published: June 2021

Context

Recent diagnostic criteria updates of the tall cell variant of papillary thyroid carcinoma (TCPTC) by the World Health Organization (WHO) have determined the inclusion of tumors with 30% to 49% of tall cells. However, the impact of tall cell percentage on papillary thyroid carcinoma (PTC) patients’ prognosis is still debated.

Objective

We aimed to evaluate whether tall cell percentage affects patient outcome in the absence of aggressive features.

Methods

Rates of aggressive features, recurrence-free survival (RFS), and distant RFS (5-year median follow-up) were compared among tumors with less than 30%, 30% to 49% and at least 50% tall cells. We also evaluated the impact of the new tall cell cutoff on patient management.

Results

Overall, 3092 tumors (15.7% of all PTCs) were collected: A total of 792 PTCs had less than 30%, 503 had 30% to 49%, and 1797 had 50% or more tall cell areas. With the new WHO definition, the number of TCPTCs increased by 28%. There were no differences in recurrence rates according to tall cell percentage. The coexistence of BRAF and TERT promoter mutations predicted a worse RFS. Considering the new definition of TCPTC, the level of risk according to the American Thyroid Association increased from low to intermediate in 4.2% of cases. However, the recurrence rate within this subgroup was comparable to low risk.

Conclusion

TCPTC and PTC with tall cell areas can be considered as a unique group with similar recurrence risk. However, whenever aggressive features are absent, tumors have a low risk of recurrence independently of tall cell percentage.
SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A
Authors: Yu Bin , Lin Qiaoyu , Huang Chao , Zhang Boyan , Wang Ying , Jiang Qing , Zhang Chuanmao , Yi Jing
Published: June 2021

Precise chromosome segregation is mediated by a well-assembled mitotic spindle, which requires balance of the kinase activity of Aurora A (AurA, also known as AURKA). However, how this kinase activity is regulated remains largely unclear. Here, using in vivo and in vitro assays, we report that conjugation of SUMO2 with AurA at K258 in early mitosis promotes the kinase activity of AurA and facilitates the binding with its activator Bora. Knockdown of the SUMO proteases SENP3 and SENP5 disrupts the deSUMOylation of AurA, leading to increased kinase activity and abnormalities in spindle assembly and chromosome segregation, which could be rescued by suppressing the kinase activity of AurA. Collectively, these results demonstrate that SENP3 and SENP5 deSUMOylate AurA to render spatiotemporal control on its kinase activity in mitosis.

This article has an associated First Person interview with the first author of the paper.